Abstract
Gastric cancer remains an important contributor to the global cancer burden ranking the 5th most common and the 4th most deadly cancer, according to the latest cancer statistics. Despite the recent advances in the treatment of gastric cancer, with combinatorial and targeted therapies, the overall survival and cure rates are still poor, in particular for patients with advanced metastatic disease. Several reasons may explain the yet unsatisfactory clinical outcome of gastric cancer disease, from biological to experimental and conceptual, which should be tackled in an integrated manner to allow the development of better therapeutic options. Drug repurposing (DR, also known as drug repositioning) is gaining considerable attention as an additional strategy to the mainstream de novo drug discovery process. DR provides suitable drugs to expand the cancer chemotherapy options because it may explore the vast number of approved agents with known safety profiles. The opportunity to use repurposed drugs is grounded in the progress of the knowledge of cancer “physiology” and the consequent identification of more targetable pathways. It is also fostered by the possibility of the combined use of computational and bioinformatic tools, drug screening automation, sequencing technologies, and chemistry. Herein, after a brief introduction to gastric cancer facts and currently approved therapies, we review the current status of DR in gastric cancer mainly focusing on non-oncological drugs (i.e., drugs approved for diseases other than cancers) that have been under pre-clinical and clinical evaluation for cancer and compare the potential advantages and limitations of DR over the traditionally de novo development process. It will also be described the main strategies used to identify potentially “repurposable” drugs and discussed the challenges ahead for DR in gastric cancer.
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References
GLOBOCAN2020 (2020) The Global Cancer Observatory (GCO). The International Agency for Research on Cancer (IARC). World Health Organization. https://gco.iarc.fr/. [cited 4 Apr 2022]
Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30. https://doi.org/10.3322/caac.21166
Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424. https://doi.org/10.3322/caac.21492
Cislo M, Filip AA, Arnold Offerhaus GJ et al (2018) Distinct molecular subtypes of gastric cancer: from Lauren to molecular pathology. Oncotarget 9(27):19427–19442. https://doi.org/10.18632/oncotarget.24827
Ajani JA, Lee J, Sano T et al (2017) Gastric adenocarcinoma. Nat Rev Dis Prim 3:17036. https://doi.org/10.1038/nrdp.2017.36
Richman DM, Tirumani SH, Hornick JL et al (2017) Beyond gastric adenocarcinoma: Multimodality assessment of common and uncommon gastric neoplasms. Abdom Radiol (NY) 42(1):124–140. https://doi.org/10.1007/s00261-016-0901-x
Kamiya S, Rouvelas I, Lindblad M et al (2018) Current trends in gastric cancer treatment in Europe. J Cancer Metastasis Treat 4:35. https://doi.org/10.20517/2394-4722.2017.76
Yin S, Wang P, Xu X et al (2019) The optimal strategy of multimodality therapies for resectable gastric cancer: evidence from a network meta-analysis. J Cancer 10(14):3094–3101. https://doi.org/10.7150/jca.30456
National Comprehensive Cancer Network® (2022) NCCN Guidelines for Gastric Cancer. Version 2.2020. 2020 [cited 2022 April 4]; Available from https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1434
Drugs Approved for Stomach (Gastric) Cancer. NIH. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/drugs/stomach
Digestive Cancers Europe—Drug Database for Digestive Cancers (2022). https://digestivecancers.eu/providing-support-to-patients-2/pharmaceutical-treatments/ [cited 2022 April 4]
National Comprehensive Cancer Network® (2022) Treatment by cancer type. [cited 2022 April 4]; Available from https://www.nccn.org/guidelines/category_1
Jomrich G, Schoppmann SF (2016) Targeted therapy in gastric cancer. Eur Surg 48(5):278–284. https://doi.org/10.1007/s10353-016-0389-1
O Reilly DM, McLaughlin AR, Ronayne C et al (2021) Access to innovative cancer medicines in gastrointestinal oncology: 2010 through 2020. J Clin Oncol 39(3_suppl):469–469. https://doi.org/10.1200/JCO.2021.39.3_suppl.469
Joshi SS, Badgwell BD (2021) Current treatment and recent progress in gastric cancer. CA Cancer J Clin 71(3):264–279. https://doi.org/10.3322/caac.21657
United States National Institutes of Health—National Library of Medicine. Clinical Trials database: https://clinicaltrials.gov/ [database on the Internet]
Pina AS, Hussain A, Roque AC (2009) An historical overview of drug discovery. Methods Mol Biol 572:3–12. https://doi.org/10.1007/978-1-60761-244-5_1
Hughes JP, Rees S, Kalindjian SB et al (2011) Principles of early drug discovery. Br J Pharmacol 162(6):1239–1249. https://doi.org/10.1111/j.1476-5381.2010.01127.x
Evens R, Kaitin K (2015) The evolution of biotechnology and its impact on health care. Health Aff (Millwood) 34(2):210–219. https://doi.org/10.1377/hlthaff.2014.1023
Liu R, Li X, Lam KS (2017) Combinatorial chemistry in drug discovery. Curr Opin Chem Biol 38:117–126. https://doi.org/10.1016/j.cbpa.2017.03.017
Report Global Trends in R&D: Overview Through 2021 (2022) IQVIA Institute for Human Data Science, 10 Feb 2022, Report No
Gashaw I, Ellinghaus P, Sommer A et al (2012) What makes a good drug target? Drug Discov Today 17(Suppl):S24–S30. https://doi.org/10.1016/j.drudis.2011.12.008
Swinney DC (2013) Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin Pharmacol Ther 93(4):299–301. https://doi.org/10.1038/clpt.2012.236
Croston GE (2017) The utility of target-based discovery. Expert Opin Drug Discov 12(5):427–429. https://doi.org/10.1080/17460441.2017.1308351
Moffat JG, Vincent F, Lee JA et al (2017) Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nat Rev Drug Discov 16(8):531–543. https://doi.org/10.1038/nrd.2017.111
Najmi A, Javed SA, Al Bratty M et al (2022) Modern approaches in the discovery and development of plant-based natural products and their analogues as potential therapeutic agents. Molecules 27(2):349. https://doi.org/10.3390/molecules27020349
Ashburn TT, Thor KB (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov 3(8):673–683. https://doi.org/10.1038/nrd1468
https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process
Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3(8):711–715. https://doi.org/10.1038/nrd1470
Khanna I (2012) Drug discovery in pharmaceutical industry: productivity challenges and trends. Drug Discov Today 17(19-20):1088–1102. https://doi.org/10.1016/j.drudis.2012.05.007
Sams-Dodd F (2013) Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift. Drug Discov Today 18(5-6):211–217. https://doi.org/10.1016/j.drudis.2012.10.010
Yue WW, Froese DS, Brennan PE (2014) The role of protein structural analysis in the next generation sequencing era. Top Curr Chem 336:67–98. https://doi.org/10.1007/128_2012_326
Waring MJ, Arrowsmith J, Leach AR et al (2015) An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nat Rev Drug Discov 14(7):475–486. https://doi.org/10.1038/nrd4609
Prasad V, De Jesus K, Mailankody S (2017) The high price of anticancer drugs: origins, implications, barriers, solutions. Nat Rev Clin Oncol 14(6):381–390. https://doi.org/10.1038/nrclinonc.2017.31
Schneider G, Clark DE (2019) Automated de novo drug design: are we nearly there yet? Angew Chem Int Ed Engl 58(32):10792–10803. https://doi.org/10.1002/anie.201814681
Pushpakom S, Iorio F, Eyers PA et al (2019) Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18(1):41–58. https://doi.org/10.1038/nrd.2018.168
Wouters OJ, McKee M, Luyten J (2020) Estimated research and development investment needed to bring a new medicine to market, 2009-2018. JAMA 323(9):844–853. https://doi.org/10.1001/jama.2020.1166
Langedijk J, Mantel-Teeuwisse AK, Slijkerman DS et al (2015) Drug repositioning and repurposing: terminology and definitions in literature. Drug Discov Today 20(8):1027–1034. https://doi.org/10.1016/j.drudis.2015.05.001
Jourdan JP, Bureau R, Rochais C et al (2020) Drug repositioning: a brief overview. J Pharm Pharmacol 72(9):1145–1151. https://doi.org/10.1111/jphp.13273
Oprea TI, Overington JP (2015) Computational and Practical Aspects of Drug Repositioning. Assay Drug Dev Technol 13(6):299–306. https://doi.org/10.1089/adt.2015.29011.tiodrrr
Gupta SC, Sung B, Prasad S et al (2013) Cancer drug discovery by repurposing: teaching new tricks to old dogs. Trends Pharmacol Sci 34(9):508–517. https://doi.org/10.1016/j.tips.2013.06.005
Gregori-Puigjane E, Mestres J (2008) A ligand-based approach to mining the chemogenomic space of drugs. Comb Chem High Throughput Screen 11(8):669–676. https://doi.org/10.2174/138620708785739952
Mestres J, Gregori-Puigjane E, Valverde S et al (2009) The topology of drug-target interaction networks: implicit dependence on drug properties and target families. Mol BioSyst 5(9):1051–1057. https://doi.org/10.1039/b905821b
Lin A, Giuliano CJ, Palladino A et al (2019) Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci Transl Med 11(509). https://doi.org/10.1126/scitranslmed.aaw8412
Jarada TN, Rokne JG, Alhajj R (2020) A review of computational drug repositioning: strategies, approaches, opportunities, challenges, and directions. J Cheminform 12(1):46. https://doi.org/10.1186/s13321-020-00450-7
Greene CS, Voight BF (2016) Pathway and network-based strategies to translate genetic discoveries into effective therapies. Hum Mol Genet 25(R2):R94–R98. https://doi.org/10.1093/hmg/ddw160
Kumar S, Kumar S (2019) Chapter 6. Molecular docking: a structure-based approach for drug repurposing. In: Roy K (ed) Silico Drug Design. Academic Press, pp 161–189
Panneerpandian P, Devanandan HJ, Marimuthu A et al (2020) Abacavir induces the transcriptional activity of YY1 and other oncogenic transcription factors in gastric cancer cells. Antivir Res 174:104695. https://doi.org/10.1016/j.antiviral.2019.104695
Zhao Y, Li JS, Guo MZ et al (2010) Inhibitory effect of S-adenosylmethionine on the growth of human gastric cancer cells in vivo and in vitro. Chinese J Cancer 29(8):752–760. https://doi.org/10.5732/cjc.010.10046
Luo J, Li YN, Wang F et al (2010) S-adenosylmethionine inhibits the growth of cancer cells by reversing the hypomethylation status of c-myc and H-ras in human gastric cancer and colon cancer. Int J Biol Sci 6(7):784–795. https://doi.org/10.7150/ijbs.6.784
Da MX, Zhang YB, Yao JB et al (2014) DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth. Braz J Med Biol Res 47(12):1021–1028
Zhang X, Zhao J, Gao X et al (2017) Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis. Exp Ther Med 13(2):595–603. https://doi.org/10.3892/etm.2016.3992
Yang MH, Ha IJ, Um JY et al (2021) Albendazole exhibits anti-neoplastic actions against gastric cancer cells by affecting STAT3 and STAT5 activation by pleiotropic mechanism(s). Biomedicines 9(4). https://doi.org/10.3390/biomedicines9040362
Salim AS (1992) Oxygen-derived free-radical scavengers prolong survival in gastric cancer. Chemotherapy 38(2):135–144. https://doi.org/10.1159/000238953
Yang Y, Fang E, Luo J et al (2019) the antioxidant alpha-lipoic acid inhibits proliferation and invasion of human gastric cancer cells via suppression of STAT3-mediated MUC4 gene expression. Oxidative Med Cell Longev 2019:3643715. https://doi.org/10.1155/2019/3643715
Ding Y, Zhang H, Zhou Z et al (2012) u-PA inhibitor amiloride suppresses peritoneal metastasis in gastric cancer. World J Surg Oncol 10:270. https://doi.org/10.1186/1477-7819-10-270
Hosogi S, Miyazaki H, Nakajima K et al (2012) An inhibitor of Na(+)/H(+) exchanger (NHE), ethyl-isopropyl amiloride (EIPA), diminishes proliferation of MKN28 human gastric cancer cells by decreasing the cytosolic Cl(-) concentration via DIDS-sensitive pathways. Cell Physiol Biochem 30(5):1241–1253. https://doi.org/10.1159/000343315
Shiozaki A, Katsurahara K, Kudou M et al (2021) Amlodipine and verapamil, voltage-gated Ca(2+) channel inhibitors, suppressed the growth of gastric cancer stem cells. Ann Surg Oncol 28(9):5400–5411. https://doi.org/10.1245/s10434-021-09645-0
Panneerpandian P, Rao DB, Ganesan K (2021) Calcium channel blockers lercanidipine and amlodipine inhibit YY1/ERK/TGF-beta mediated transcription and sensitize the gastric cancer cells to doxorubicin. Toxicol in Vitro 74:105152. https://doi.org/10.1016/j.tiv.2021.105152
Gong Z, Ma J, Su H et al (2018) Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer. Int J Clin Oncol 23(4):659–670. https://doi.org/10.1007/s10147-018-1242-2
Shokrzadeh M, Mohammadpour A, Modanloo M et al (2019) Cytotoxic effects of aripiprazole on Mkn45 and Nih3t3 cell lines and genotoxic effects on human peripheral blood lymphocytes. Arq Gastroenterol 56(2):155–159. https://doi.org/10.1590/S0004-2803.201900000-31
Zhou X, Sun WJ, Wang WM et al (2013) Artesunate inhibits the growth of gastric cancer cells through the mechanism of promoting oncosis both in vitro and in vivo. Anti-Cancer Drugs 24(9):920–927. https://doi.org/10.1097/CAD.0b013e328364a109
Zhang P, Luo HS, Li M et al (2015) Artesunate inhibits the growth and induces apoptosis of human gastric cancer cells by downregulating COX-2. Onco Targets Ther 8:845–854. https://doi.org/10.2147/OTT.S81041
Wang L, Liu L, Wang J et al (2017) Inhibitory effect of artesunate on growth and apoptosis of gastric cancer cells. Arch Med Res 48(7):623–630. https://doi.org/10.1016/j.arcmed.2018.03.004
Zhu GH, Wong BC, Eggo MC et al (1999) Non-steroidal anti-inflammatory drug-induced apoptosis in gastric cancer cells is blocked by protein kinase C activation through inhibition of c-myc. Br J Cancer 79(3-4):393–400. https://doi.org/10.1038/sj.bjc.6690062
Zhou XM, Wong BC, Fan XM et al (2001) Non-steroidal anti-inflammatory drugs induce apoptosis in gastric cancer cells through up-regulation of bax and bak. Carcinogenesis 22(9):1393–1397. https://doi.org/10.1093/carcin/22.9.1393
Azarschab P, Al-Azzeh E, Kornberger W et al (2001) Aspirin promotes TFF2 gene activation in human gastric cancer cell lines. FEBS Lett 488(3):206–210. https://doi.org/10.1016/s0014-5793(00)02422-4
Tang C, Wang C, Tang L (2003) Effects of combined octreotide and aspirin on the growth of gastric cancer. Chin Med J 116(3):373–377
Gu Q, Wang JD, Xia HH et al (2005) Activation of the caspase-8/Bid and Bax pathways in aspirin-induced apoptosis in gastric cancer. Carcinogenesis 26(3):541–546. https://doi.org/10.1093/carcin/bgh345
Becker JC, Muller-Tidow C, Stolte M et al (2006) Acetylsalicylic acid enhances antiproliferative effects of the EGFR inhibitor gefitinib in the absence of activating mutations in gastric cancer. Int J Oncol 29(3):615–623. https://doi.org/10.3892/ijo.29.3.615
Redlak MJ, Power JJ, Miller TA (2007) Aspirin-induced apoptosis in human gastric cancer epithelial cells: relationship with protein kinase C signaling. Dig Dis Sci 52(3):810–816. https://doi.org/10.1007/s10620-006-9577-3
Pantziarka P, Verbaanderd C, Sukhatme V et al (2018) ReDO_DB: the repurposing drugs in oncology database. Ecancermedicalscience 12:886. https://doi.org/10.3332/ecancer.2018.886
Zhang YJ, Dai Q, Wu SM et al (2008) Susceptibility for NSAIDs-induced apoptosis correlates to p53 gene status in gastric cancer cells. Cancer Investig 26(9):868–877. https://doi.org/10.1080/07357900801944872
Yang L, Zhu H, Liu D et al (2011) Aspirin suppresses growth of human gastric carcinoma cell by inhibiting survivin expression. J Biomed Res 25(4):246–253. https://doi.org/10.1016/S1674-8301(11)60033-X
Dong H, Liu G, Jiang B et al (2014) The effects of aspirin plus cisplatin on SGC7901/CDDP cells in vitro. Biomed Rep 2(3):344–348. https://doi.org/10.3892/br.2014.241
Akrami H, Aminzadeh S, Fallahi H (2015) Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell. Tumour Biol 36(5):3237–3243. https://doi.org/10.1007/s13277-014-2952-3
Li XF, Xu BZ, Wang SZ (2016) Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice. Oncol Lett 12(5):3183–3186. https://doi.org/10.3892/ol.2016.5067
Mikami J, Kurokawa Y, Takahashi T et al (2016) Antitumor effect of antiplatelet agents in gastric cancer cells: an in vivo and in vitro study. Gastric Cancer 19(3):817–826. https://doi.org/10.1007/s10120-015-0556-2
Zhang W, Tan Y, Ma H (2017) Combined aspirin and apatinib treatment suppresses gastric cancer cell proliferation. Oncol Lett 14(5):5409–5417. https://doi.org/10.3892/ol.2017.6858
Shah S, Pocard M, Mirshahi M (2019) Targeting the differentiation of gastric cancer cells (KATOIII) downregulates epithelial mesenchymal and cancer stem cell markers. Oncol Rep 42(2):670–678. https://doi.org/10.3892/or.2019.7198
Bayer (2020) EffectiveNess of low-dose Aspirin in GastrointEstinal cancer prevention –United Kingdom (“ENgAGE—UK”): a cohort study on the risk of gastric and oesophageal cancer among new users of low-dose Aspirin using the THIN database in the UK—observational study results synopsis (ID20326). Report no
Shami JJP, Zhao J, Pathadka S et al (2022) Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study. BMJ Open 12(2):e050510. https://doi.org/10.1136/bmjopen-2021-050510
Zhang X, Zhang Y, He Z et al (2019) Chronic stress promotes gastric cancer progression and metastasis: an essential role for ADRB2. Cell Death Dis 10(11):788. https://doi.org/10.1038/s41419-019-2030-2
Lee S, Lee HJ, Kang H et al (2019) Trastuzumab induced chemobrain, atorvastatin rescued chemobrain with enhanced anticancer effect and without hair loss-side effect. J Clin Med 8(2):234. https://doi.org/10.3390/jcm8020234
Wei J, Peng K, Zhu J et al (2020) Geranylgeranylation promotes proliferation, migration and invasion of gastric cancer cells through the YAP signaling pathway. Am J Transl Res 12(9):5296–5307
Zou P, Chen M, Ji J et al (2015) Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer. Oncotarget 6(34):36505–36521. https://doi.org/10.18632/oncotarget.5364
Kim TW, Lee SJ, Kim JT et al (2016) Kallikrein-related peptidase 6 induces chemotherapeutic resistance by attenuating auranofin-induced cell death through activation of autophagy in gastric cancer. Oncotarget 7(51):85332–85348. https://doi.org/10.18632/oncotarget.13352
Zhou X, Zhang Y, Li Y et al (2012) Azithromycin synergistically enhances anti-proliferative activity of vincristine in cervical and gastric cancer cells. Cancers 4(4):1318–1332. https://doi.org/10.3390/cancers4041318
Thilakasiri P, Huynh J, Poh AR et al (2019) Repurposing the selective estrogen receptor modulator bazedoxifene to suppress gastrointestinal cancer growth. EMBO Mol Med 11(4). https://doi.org/10.15252/emmm.201809539
Leng ZG, Lin SJ, Wu ZR et al (2017) Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death. Autophagy 13(8):1404–1419. https://doi.org/10.1080/15548627.2017.1328347
Takahashi M, Yanoma S, Yamamoto Y et al (1998) Combined effect of CDDP and caffeine against human gastric cell line in vivo. Anticancer Res 18(6A):4399–4401
Liu H, Zhou Y, Tang L (2017) Caffeine induces sustained apoptosis of human gastric cancer cells by activating the caspase 9/caspase 3 signalling pathway. Mol Med Rep 16(3):2445–2454. https://doi.org/10.3892/mmr.2017.6894
Liu H, Song J, Zhou Y et al (2019) Methylxanthine derivatives promote autophagy in gastric cancer cells targeting PTEN. Anti-Cancer Drugs 30(4):347–355. https://doi.org/10.1097/CAD.0000000000000724
Huang W, Wu YL, Zhong J et al (2008) Angiotensin II type 1 receptor antagonist suppress angiogenesis and growth of gastric cancer xenografts. Dig Dis Sci 53(5):1206–1210. https://doi.org/10.1007/s10620-007-0009-9
Kinoshita J, Fushida S, Harada S et al (2009) Local angiotensin II-generation in human gastric cancer: correlation with tumor progression through the activation of ERK1/2, NF-kappaB and survivin. Int J Oncol 34(6):1573–1582. https://doi.org/10.3892/ijo_00000287
Okazaki M, Fushida S, Harada S et al (2014) The angiotensin II type 1 receptor blocker candesartan suppresses proliferation and fibrosis in gastric cancer. Cancer Lett 355(1):46–53. https://doi.org/10.1016/j.canlet.2014.09.019
Zhang X, Qin Y, Pan Z et al (2019) Cannabidiol induces cell cycle arrest and cell apoptosis in human gastric cancer SGC-7901 cells. Biomolecules 9(8). https://doi.org/10.3390/biom9080302
Jeong S, Jo MJ, Yun HK et al (2019) Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer. Cell Death Dis 10(11):846. https://doi.org/10.1038/s41419-019-2001-7
Wang L, Cai SR, Zhang CH et al (2008) Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers on lymphangiogenesis of gastric cancer in a nude mouse model. Chin Med J 121(21):2167–2171
Hu PJ, Yu J, Zeng ZR et al (2004) Chemoprevention of gastric cancer by celecoxib in rats. Gut 53(2):195–200. https://doi.org/10.1136/gut.2003.021477
Fu SL, Wu YL, Zhang YP et al (2004) Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer. World J Gastroenterol 10(13):1971–1974. https://doi.org/10.3748/wjg.v10.i13.1971
Wu YL, Fu SL, Zhang YP et al (2005) Cyclooxygenase-2 inhibitors suppress angiogenesis and growth of gastric cancer xenografts. Biomed Pharmacother 59(Suppl 2):S289–S292. https://doi.org/10.1016/s0753-3322(05)80048-4
Yu J, Tang BD, Leung WK et al (2005) Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: implications on chemoprevention. World J Gastroenterol 11(1):41–45. https://doi.org/10.3748/wjg.v11.i1.41
Cho SJ, Kim N, Kim JS et al (2007) The anti-cancer effect of COX-2 inhibitors on gastric cancer cells. Dig Dis Sci 52(7):1713–1721. https://doi.org/10.1007/s10620-007-9787-3
Pang RP, Zhou JG, Zeng ZR et al (2007) Celecoxib induces apoptosis in COX-2 deficient human gastric cancer cells through Akt/GSK3beta/NAG-1 pathway. Cancer Lett 251(2):268–277. https://doi.org/10.1016/j.canlet.2006.11.032
Wang CH, Zheng WB, Qiang O et al (2009) Effects of non-cytotoxic drugs on the growth of multidrug-resistance human gastric carcinoma cell line. J Dig Dis 10(2):91–98. https://doi.org/10.1111/j.1751-2980.2009.00370.x
Saito Y, Suzuki H, Imaeda H et al (2013) The tumor suppressor microRNA-29c is downregulated and restored by celecoxib in human gastric cancer cells. Int J Cancer 132(8):1751–1760. https://doi.org/10.1002/ijc.27862
Wang YJ, Niu XP, Yang L et al (2013) Effects of celecoxib on cycle kinetics of gastric cancer cells and protein expression of cytochrome C and caspase-9. Asian Pac J Cancer Prev 14(4):2343–2347. https://doi.org/10.7314/apjcp.2013.14.4.2343
Liu T, Liang X, Li B et al (2013) Telomerase reverse transcriptase inhibition stimulates cyclooxygenase 2 expression in cancer cells and synergizes with celecoxib to exert anti-cancer effects. Br J Cancer 108(11):2272–2280. https://doi.org/10.1038/bjc.2013.208
Chen M, Yu L, Gu C et al (2013) Celecoxib antagonizes the cytotoxic effect of cisplatin in human gastric cancer cells by decreasing intracellular cisplatin accumulation. Cancer Lett 329(2):189–196. https://doi.org/10.1016/j.canlet.2012.10.030
Liu M, Li CM, Chen ZF et al (2014) Celecoxib regulates apoptosis and autophagy via the PI3K/Akt signaling pathway in SGC-7901 gastric cancer cells. Int J Mol Med 33(6):1451–1458. https://doi.org/10.3892/ijmm.2014.1713
Meng C, Lu Z, Fang M et al (2014) Effect of celecoxib combined with chemotherapy drug on malignant biological behaviors of gastric cancer. Int J Clin Exp Pathol 7(11):7622–7632
Xu HB, Shen FM, Lv QZ (2015) Celecoxib enhanced the cytotoxic effect of cisplatin in drug-resistant human gastric cancer cells by inhibition of cyclooxygenase-2. Eur J Pharmacol 769:1–7. https://doi.org/10.1016/j.ejphar.2015.09.025
Zhang L, Tong Y, Zhang X et al (2015) Arsenic sulfide combined with JQ1, chemotherapy agents, or celecoxib inhibit gastric and colon cancer cell growth. Drug Des Devel Ther 9:5851–5862. https://doi.org/10.2147/DDDT.S92943
Zhang XQ, Sun XE, Liu WD et al (2015) Synergic effect between 5-fluorouracil and celecoxib on hypoxic gastric cancer cells. Mol Med Rep 11(2):1160–1166. https://doi.org/10.3892/mmr.2014.2783
Zhang XQ, Zhang HM, Sun XE et al (2015) Inhibitory effects and mechanism of 5-fluorouracil combined with celecoxib on human gastric cancer xenografts in nude mice. Exp Ther Med 9(1):105–111. https://doi.org/10.3892/etm.2014.2077
Xu HB, Shen FM, Lv QZ (2016) Celecoxib enhanced the cytotoxic effect of cisplatin in chemo-resistant gastric cancer xenograft mouse models through a cyclooxygenase-2-dependent manner. Eur J Pharmacol 776:1–8. https://doi.org/10.1016/j.ejphar.2016.02.035
Li Q, Peng J, Liu T et al (2017) Effects of celecoxib on cell apoptosis and Fas, FasL and Bcl-2 expression in a BGC-823 human gastric cancer cell line. Exp Ther Med 14(3):1935–1940. https://doi.org/10.3892/etm.2017.4769
Lin XM, Li S, Zhou C et al (2019) Cisplatin induces chemoresistance through the PTGS2-mediated anti-apoptosis in gastric cancer. Int J Biochem Cell Biol 116:105610. https://doi.org/10.1016/j.biocel.2019.105610
Choi SM, Cho YS, Park G et al (2021) Celecoxib induces apoptosis through Akt inhibition in 5-fluorouracil-resistant gastric cancer cells. Toxicol Res 37(1):25–33. https://doi.org/10.1007/s43188-020-00044-3
Badalanloo K, Naji T, Ahmadi R (2022) Cytotoxic and apoptotic effects of celecoxib and topotecan on AGS and HEK 293 cell lines. J Gastrointest Cancer 53(1):99–104. https://doi.org/10.1007/s12029-020-00434-8
Huang MT, Chen ZX, Wei B et al (2007) Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide. Acta Pharmacol Sin 28(11):1842–1850. https://doi.org/10.1111/j.1745-7254.2007.00652.x
Zhou Y, Ran J, Tang C et al (2007) Effect of celecoxib on E-cadherin, VEGF, microvessel density and apoptosis in gastric cancer. Cancer Biol Ther 6(2):269–275. https://doi.org/10.4161/cbt.6.2.3629
Han X, Li H, Su L et al (2014) Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer. Biomed Rep 2(2):183–187. https://doi.org/10.3892/br.2013.209
Guo Q, Liu X, Lu L et al (2017) Comprehensive evaluation of clinical efficacy and safety of celecoxib combined with chemotherapy in management of gastric cancer. Medicine (Baltimore) 96(51):e8857. https://doi.org/10.1097/MD.0000000000008857
Guo Q, Li Q, Wang J et al (2019) A comprehensive evaluation of clinical efficacy and safety of celecoxib in combination with chemotherapy in metastatic or postoperative recurrent gastric cancer patients: a preliminary, three-center, clinical trial study. Medicine (Baltimore) 98(27):e16234. https://doi.org/10.1097/MD.0000000000016234
Brew T, Bougen-Zhukov N, Mitchell W et al (2021) Loss of E-cadherin leads to druggable vulnerabilities in sphingolipid metabolism and vesicle trafficking. Cancers 14(1). https://doi.org/10.3390/cancers14010102
Yan H, Sun Y, Wu Q et al (2019) PELP1 suppression inhibits gastric cancer through downregulation of c-Src-PI3K-ERK pathway. Front Oncol 9:1423. https://doi.org/10.3389/fonc.2019.01423
Hahm KB, Park IS, Kim HC et al (1996) Comparison of antiproliferative effects of 1-histamine-2 receptor antagonists, cimetidine, ranitidine, and famotidine, in gastric cancer cells. Int J Immunopharmacol 18(6-7):393–399. https://doi.org/10.1016/s0192-0561(96)00044-6
Jiang CG, Liu FR, Yu M et al (2010) Cimetidine induces apoptosis in gastric cancer cells in vitro and inhibits tumor growth in vivo. Oncol Rep 23(3):693–700. https://doi.org/10.3892/or_00000686
Liu FR, Jiang CG, Li YS et al (2011) Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression. Int J Mol Med 27(4):537–544. https://doi.org/10.3892/ijmm.2011.618
Zhang L, Li Q, Xu J et al (2020) Cimetidine promotes STUB1-mediated degradation of tumoral FOXP3 by activating PI3K-Akt pathway in gastric cancer. Ann Transl Med 8(20):1304. https://doi.org/10.21037/atm-20-6070
Tonnesen H, Knigge U, Bulow S et al (1988) Effect of cimetidine on survival after gastric cancer. Lancet 2(8618):990–992. https://doi.org/10.1016/s0140-6736(88)90743-x
Langman MJ, Dunn JA, Whiting JL et al (1999) Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer. British Stomach Cancer Group. Br J Cancer 81(8):1356–1362. https://doi.org/10.1038/sj.bjc.6690457
Lin ZY, Kuo CH, Wu DC et al (2016) Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines. Kaohsiung J Med Sci 32(2):68–73. https://doi.org/10.1016/j.kjms.2015.12.006
Zhang T, Chen W, Jiang X et al (2019) Anticancer effects and underlying mechanism of Colchicine on human gastric cancer cell lines in vitro and in vivo. Biosci Rep 39(1). https://doi.org/10.1042/BSR20181802
Piontek M, Porschen R (1994) Growth inhibition of human gastrointestinal cancer cells by cyclosporin A. J Cancer Res Clin Oncol 120(12):695–699. https://doi.org/10.1007/BF01194265
Morisaki T, Matsunaga H, Beppu K et al (2000) A combination of cyclosporin-A (CsA) and interferon-gamma (INF-gamma) induces apoptosis in human gastric carcinoma cells. Anticancer Res 20(5B):3363–3373
Carl-McGrath S, Ebert MP, Lendeckel U et al (2007) Expression of the local angiotensin II system in gastric cancer may facilitate lymphatic invasion and nodal spread. Cancer Biol Ther 6(8):1218–1226. https://doi.org/10.4161/cbt.6.8.4412
Choi JH, Kim JS, Won YW et al (2016) The potential of deferasirox as a novel therapeutic modality in gastric cancer. World J Surg Oncol 14:77. https://doi.org/10.1186/s12957-016-0829-1
Kim JL, Lee DH, Na YJ et al (2016) Iron chelator-induced apoptosis via the ER stress pathway in gastric cancer cells. Tumour Biol 37(7):9709–9719. https://doi.org/10.1007/s13277-016-4878-4
Fujii T, Katoh M, Ootsubo M et al (2022) Cardiac glycosides stimulate endocytosis of GLUT1 via intracellular Na(+), K(+)-ATPase alpha3-isoform in human cancer cells. J Cell Physiol. https://doi.org/10.1002/jcp.30762
Sakaguchi Y, Maehara Y, Emi Y et al (1991) Dipyridamole combination chemotherapy can be used safely in treating gastric cancer patients. Anti-Cancer Drugs 2(2):139–143. https://doi.org/10.1097/00001813-199104000-00003
Wang IH, Huang TT, Chen JL et al (2020) Mevalonate pathway enzyme HMGCS1 contributes to gastric cancer progression. Cancers 12(5). https://doi.org/10.3390/cancers12051088
Kohnoe S, Maehara Y, Takahashi I et al (1998) Treatment of advanced gastric cancer with 5-fluorouracil and cisplatin in combination with dipyridamole. Int J Oncol 13(6):1203–1206. https://doi.org/10.3892/ijo.13.6.1203
Zhang J, Pu K, Bai S et al (2020) The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-kappaB pathways. J Int Med Res 48(6):300060520925996. https://doi.org/10.1177/0300060520925996
Wang L, Chai X, Wan R et al (2020) Disulfiram Chelated With Copper Inhibits the Growth of Gastric Cancer Cells by Modulating Stress Response and Wnt/beta-catenin Signaling. Front Oncol 10:595718. https://doi.org/10.3389/fonc.2020.595718
Du C, Guan X, Liu Y et al (2022) Disulfiram/copper induces antitumor activity against gastric cancer cells in vitro and in vivo by inhibiting S6K1 and c-Myc. Cancer Chemother Pharmacol 89(4):451–458. https://doi.org/10.1007/s00280-022-04398-3
Liu Y, Guan X, Wang M et al (2022) Disulfiram/Copper induces antitumor activity against gastric cancer via the ROS/MAPK and NPL4 pathways. Bioengineered 13(3):6579–6589. https://doi.org/10.1080/21655979.2022.2038434
Pandian J, Panneerpandian P, Devanandan HJ et al (2020) Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients. Ann N Y Acad Sci 1467(1):94–111. https://doi.org/10.1111/nyas.14288
Tang C, Yang L, Jiang X et al (2014) Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells. Biochem Biophys Res Commun 446(1):105–112. https://doi.org/10.1016/j.bbrc.2014.02.043
Barranco SC, Ford PJ, Townsend CM Jr (1986) Heterogeneous survival responses of human gastric cancer clones to alpha difluoromethylornithine in vitro. Investig New Drugs 4(4):337–345. https://doi.org/10.1007/BF00173506
Barranco SC, Ford PJ, Townsend CM Jr (1986) Cell cycle kinetics responses of human stomach cancer cells to reduction in polyamine levels by treatment with alpha difluoromethylornithine in vitro. Investig New Drugs 4(4):347–357. https://doi.org/10.1007/BF00173507
Fujimoto S, Igarashi K, Shrestha RD et al (1986) Combined therapy of polyamine antimetabolites and antitumor drugs for human gastric cancer xenotransplanted into nude mice. Jpn J Surg 16(2):133–139. https://doi.org/10.1007/BF02471083
Fujimoto S, Shrestha RD, Ohta M et al (1987) Enhanced antitumor efficacy with a combination of hyperthermochemotherapy and thermosensitization with polyamine antimetabolites in nude mice. Jpn J Surg 17(2):110–117. https://doi.org/10.1007/BF02470650
Shrestha RD, Fujimoto S, Okui K (1987) Contradictory antitumor efficacies produced by the combination of DNA attacking drugs and polyamine antimetabolites. Jpn J Surg 17(4):263–268. https://doi.org/10.1007/BF02470698
Upp JR Jr, Beauchamp RD, Townsend CM Jr et al (1988) Inhibition of human gastric adenocarcinoma xenograft growth in nude mice by alpha-difluoromethylornithine. Cancer Res 48(11):3265–3269
Barranco SC, Townsend CM Jr, Ho BY et al (1990) Schedule dependent potentiation of antitumor drug effects by alpha-difluoromethylornithine in human gastric carcinoma cells in vitro. Investig New Drugs 8(Suppl 1):S9–S18. https://doi.org/10.1007/BF00171979
Kubota S (1992) Synergistic antiproliferative activity of human fibroblast interferon in combination with alpha-difluoromethylornithine against human gastric cancer cells in vitro. Cancer 69(10):2395–2399. https://doi.org/10.1002/1097-0142(19920515)69:10<2395::aid-cncr2820691002>3.0.co;2-h
Shrestha RD, Fujimoto S, Okui K (1992) A novel anticancer treatment for xenoplanted human gastric cancer using polyamine antimetabolites in a low polyamine diet. Surg Today 22(2):137–142. https://doi.org/10.1007/BF00311338
Takahashi Y, Mai M, Nishioka K (2000) alpha-difluoromethylornithine induces apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in a human gastric cancer model. Int J Cancer 85(2):243–247
Chen M, Lu J, Wei W et al (2018) Effects of proton pump inhibitors on reversing multidrug resistance via downregulating V-ATPases/PI3K/Akt/mTOR/HIF-1alpha signaling pathway through TSC1/2 complex and Rheb in human gastric adenocarcinoma cells in vitro and in vivo. Onco Targets Ther 11:6705–6722. https://doi.org/10.2147/OTT.S161198
Xu Q, Jia X, Wu Q et al (2020) Esomeprazole affects the proliferation, metastasis, apoptosis and chemosensitivity of gastric cancer cells by regulating lncRNA/circRNA-miRNA-mRNA ceRNA networks. Oncol Lett 20(6):329. https://doi.org/10.3892/ol.2020.12193
Du J, Xu Q, Zhao H et al (2022) PI3K inhibitor 3-MA promotes the antiproliferative activity of esomeprazole in gastric cancer cells by downregulating EGFR via the PI3K/FOXO3a pathway. Biomed Pharmacother 148:112665. https://doi.org/10.1016/j.biopha.2022.112665
Hinsenkamp I, Schulz S, Roscher M et al (2016) Inhibition of rho-associated kinase 1/2 attenuates tumor growth in murine gastric cancer. Neoplasia 18(8):500–511. https://doi.org/10.1016/j.neo.2016.07.002
Chen L, Peng J, Wang Y et al (2020) Fenofibrate-induced mitochondrial dysfunction and metabolic reprogramming reversal: the anti-tumor effects in gastric carcinoma cells mediated by the PPAR pathway. Am J Transl Res 12(2):428–446
Zheng T, Meng X, Wang J et al (2010) PTEN- and p53-mediated apoptosis and cell cycle arrest by FTY720 in gastric cancer cells and nude mice. J Cell Biochem 111(1):218–228. https://doi.org/10.1002/jcb.22691
Khing TM, Po WW, Sohn UD (2019) Fluoxetine enhances anti-tumor activity of paclitaxel in gastric adenocarcinoma cells by triggering apoptosis and necroptosis. Anticancer Res 39(11):6155–6163. https://doi.org/10.21873/anticanres.13823
Khin PP, Po WW, Thein W et al (2020) Apoptotic effect of fluoxetine through the endoplasmic reticulum stress pathway in the human gastric cancer cell line AGS. Naunyn Schmiedeberg’s Arch Pharmacol 393(4):537–549. https://doi.org/10.1007/s00210-019-01739-7
Po WW, Thein W, Khin PP et al (2020) Fluoxetine simultaneously induces both apoptosis and autophagy in human gastric adenocarcinoma cells. Biomol Ther (Seoul) 28(2):202–210. https://doi.org/10.4062/biomolther.2019.103
Qian X, Li J, Ding J et al (2008) Glibenclamide exerts an antitumor activity through reactive oxygen species-c-jun NH2-terminal kinase pathway in human gastric cancer cell line MGC-803. Biochem Pharmacol 76(12):1705–1715. https://doi.org/10.1016/j.bcp.2008.09.009
Wang W, Liu L, Zhou Y et al (2019) Hydroxychloroquine enhances the antitumor effects of BC001 in gastric cancer. Int J Oncol 55(2):405–414. https://doi.org/10.3892/ijo.2019.4824
Bonelli P, Tuccillo FM, Calemma R et al (2011) Changes in the gene expression profile of gastric cancer cells in response to ibuprofen: a gene pathway analysis. Pharmacogenomics J 11(6):412–428. https://doi.org/10.1038/tpj.2010.55
Akrami H, Moradi B, Borzabadi Farahani D et al (2018) Ibuprofen reduces cell proliferation through inhibiting Wnt/beta catenin signaling pathway in gastric cancer stem cells. Cell Biol Int 42(8):949–958. https://doi.org/10.1002/cbin.10959
Ding XW, Luo HS, Jin X et al (2007) Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines. Med Oncol 24(3):345–350. https://doi.org/10.1007/s12032-007-0015-y
Sawaoka H, Kawano S, Tsuji S et al (1998) Effects of NSAIDs on proliferation of gastric cancer cells in vitro: possible implication of cyclooxygenase-2 in cancer development. J Clin Gastroenterol 27(Suppl 1):S47–S52. https://doi.org/10.1097/00004836-199800001-00009
Chiou SK, Hoa N, Hodges A et al (2014) Indomethacin promotes apoptosis in gastric cancer cells through concomitant degradation of Survivin and Aurora B kinase proteins. Apoptosis 19(9):1378–1388. https://doi.org/10.1007/s10495-014-1002-3
Ito H, Matsui H, Hirayama A et al (2016) Reactive oxygen species induced by non-steroidal anti-inflammatory drugs enhance the effects of photodynamic therapy in gastric cancer cells. J Clin Biochem Nutr 58(3):180–185. https://doi.org/10.3164/jcbn.15-124
Vallecillo-Hernandez J, Barrachina MD, Ortiz-Masia D et al (2018) Indomethacin disrupts autophagic flux by inducing lysosomal dysfunction in gastric cancer cells and increases their sensitivity to cytotoxic drugs. Sci Rep 8(1):3593. https://doi.org/10.1038/s41598-018-21455-1
Mazumder S, De R, Debsharma S et al (2019) Indomethacin impairs mitochondrial dynamics by activating the PKCzeta-p38-DRP1 pathway and inducing apoptosis in gastric cancer and normal mucosal cells. J Biol Chem 294(20):8238–8258. https://doi.org/10.1074/jbc.RA118.004415
Hara M, Nagasaki T, Shiga K et al (2016) Suppression of cancer-associated fibroblasts and endothelial cells by itraconazole in bevacizumab-resistant gastrointestinal cancer. Anticancer Res 36(1):169–177
Hu Q, Hou YC, Huang J et al (2017) Itraconazole induces apoptosis and cell cycle arrest via inhibiting Hedgehog signaling in gastric cancer cells. J Exp Clin Cancer Res 36(1):50. https://doi.org/10.1186/s13046-017-0526-0
Lan K, Yan R, Zhu K et al (2018) Itraconazole inhibits the proliferation of gastric cancer cells in vitro and improves patient survival. Oncol Lett 16(3):3651–3657. https://doi.org/10.3892/ol.2018.9072
Zhao S, Shao L, Wang Y et al (2020) Ketamine exhibits anti-gastric cancer activity via induction of apoptosis and attenuation of PI3K/Akt/mTOR. Arch Med Sci 16(5):1140–1149. https://doi.org/10.5114/aoms.2019.85146
Miwa H, Ono F, Moriyama M et al (1980) Immunochemotherapy of gastric cancer with levamisole. Acta Med Okayama 34(4):275–281. https://doi.org/10.18926/AMO/30518
Hattori T, Niimoto M, Toge T et al (1983) Effects of Levamisole in adjuvant immunochemotherapy for gastric cancer; a prospective randomized controlled study. Jpn J Surg 13(6):480–485. https://doi.org/10.1007/BF02469490
Niimoto M, Hattori T, Ito I et al (1984) Levamisole in postoperative adjuvant immunochemotherapy for gastric cancer. A randomized controlled study of the MMC + Tegafur regimen with or without levamisole. Report I. Cancer Immunol Immunother 18(1):13–18. https://doi.org/10.1007/BF00205393
Group TIGTS (1988) Adjuvant treatments following curative resection for gastric cancer. The Italian Gastrointestinal Tumor Study Group. Br J Surg 75(11):1100–1104. https://doi.org/10.1002/bjs.1800751117
Choi JS, Lee KH, Ahn MJ et al (1997) A randomized trial comparing cisplatin plus 5-fluorouracil with or without levamisole in operable gastric cancer. Korean J Intern Med 12(2):155–162. https://doi.org/10.3904/kjim.1997.12.2.155
Burch PA, Keppen MD, Schroeder G et al (1999) North Central Cancer Treatment Group Phase II study of 5-fluorouracil and high-dose levamisole for gastric and gastroesophageal cancer using survival as the primary endpoint of efficacy. Am J Clin Oncol 22(5):505–508. https://doi.org/10.1097/00000421-199910000-00017
Yang W, Cai J, Zhang H et al (2018) Effects of lidocaine and ropivacaine on gastric cancer cells through down-regulation of ERK1/2 phosphorylation in vitro. Anticancer Res 38(12):6729–6735. https://doi.org/10.21873/anticanres.13042
Ye L, Zhang Y, Chen YJ et al (2019) Anti-tumor effects of lidocaine on human gastric cancer cells in vitro. Bratisl Lek Listy 120(3):212–217. https://doi.org/10.4149/BLL_2019_036
Sui H, Lou A, Li Z et al (2019) Lidocaine inhibits growth, migration and invasion of gastric carcinoma cells by up-regulation of miR-145. BMC Cancer 19(1):233. https://doi.org/10.1186/s12885-019-5431-9
Zhang X, Gu G, Li X et al (2020) Lidocaine alleviates cisplatin resistance and inhibits migration of MGC-803/DDP cells through decreasing miR-10b. Cell Cycle 19(19):2530–2537. https://doi.org/10.1080/15384101.2020.1809914
Zeng W, Xing ZT, Tan MY et al (2021) Lidocaine suppresses the malignant behavior of gastric cancer cells via the c-Met/c-Src pathway. Exp Ther Med 21(5):424. https://doi.org/10.3892/etm.2021.9868
Guan E, Liu H, Xu N (2021) Lidocaine suppresses gastric cancer development through Circ_ANO5/miR-21-5p/LIFR Axis. Dig Dis Sci. 67(6):2244–2256. https://doi.org/10.1007/s10620-021-07055-6
Huang MM, Guo AB, Sun JF et al (2014) Angiotensin II promotes the progression of human gastric cancer. Mol Med Rep 9(3):1056–1060. https://doi.org/10.3892/mmr.2014.1891
Rha SY, Noh SH, Kim TS et al (1999) Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer. Int J Mol Med 4(2):203–212. https://doi.org/10.3892/ijmm.4.2.203
Kang WK, Lee I, Park C (2005) Characterization of RhoA-mediated chemoresistance in gastric cancer cells. Cancer Res Treat 37(4):251–256. https://doi.org/10.4143/crt.2005.37.4.251
Gibot L, Follet J, Metges JP et al (2009) Human caspase 7 is positively controlled by SREBP-1 and SREBP-2. Biochem J 420(3):473–483. https://doi.org/10.1042/BJ20082057
Follet J, Remy L, Hesry V et al (2011) Adaptation to statins restricts human tumour growth in Nude mice. BMC Cancer 11:491. https://doi.org/10.1186/1471-2407-11-491
Follet J, Corcos L, Baffet G et al (2012) The association of statins and taxanes: an efficient combination trigger of cancer cell apoptosis. Br J Cancer 106(4):685–692. https://doi.org/10.1038/bjc.2012.6
Cheng-Qian Y, Xin-Jing W, Wei X et al (2014) Lovastatin inhibited the growth of gastric cancer cells. Hepato-Gastroenterology 61(129):1–4
Lin L, Liu Y, Pan C et al (2019) Gastric cancer cells escape metabolic stress via the DLC3/MACC1 axis. Theranostics 9(7):2100–2114. https://doi.org/10.7150/thno.29538
Zhang L, Kang W, Lu X et al (2019) Weighted gene co-expression network analysis and connectivity map identifies lovastatin as a treatment option of gastric cancer by inhibiting HDAC2. Gene 681:15–25. https://doi.org/10.1016/j.gene.2018.09.040
Pereira PMR, Mandleywala K, Ragupathi A et al (2019) Temporal modulation of HER2 membrane availability increases pertuzumab uptake and pretargeted molecular imaging of gastric tumors. J Nucl Med 60(11):1569–1578. https://doi.org/10.2967/jnumed.119.225813
Alzeeb G, Arzur D, Trichet V et al (2022) Gastric cancer cell death analyzed by live cell imaging of spheroids. Sci Rep 12(1):1488. https://doi.org/10.1038/s41598-022-05426-1
Kim WS, Kim MM, Choi HJ et al (2001) Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Investig New Drugs 19(1):81–83. https://doi.org/10.1023/a:1006481423298
Yamakawa N, Suemasu S, Kimoto A et al (2010) Low direct cytotoxicity of loxoprofen on gastric mucosal cells. Biol Pharm Bull 33(3):398–403. https://doi.org/10.1248/bpb.33.398
Mencarelli A, Graziosi L, Renga B et al (2013) CCR5 antagonism by maraviroc reduces the potential for gastric cancer cell dissemination. Transl Oncol 6(6):784–793. https://doi.org/10.1593/tlo.13499
Pinto LC, Soares BM, Pinheiro Jde J et al (2015) The anthelmintic drug mebendazole inhibits growth, migration and invasion in gastric cancer cell model. Toxicol in Vitro 29(8):2038–2044. https://doi.org/10.1016/j.tiv.2015.08.007
Celestino Pinto L, de Fatima Aquino Moreira-Nunes C, Soares BM et al (2017) Mebendazole, an antiparasitic drug, inhibits drug transporters expression in preclinical model of gastric peritoneal carcinomatosis. Toxicol in Vitro 43:87–91. https://doi.org/10.1016/j.tiv.2017.06.007
Pinto LC, Mesquita FP, Soares BM et al (2019) Mebendazole induces apoptosis via C-MYC inactivation in malignant ascites cell line (AGP01). Toxicol in Vitro 60:305–312. https://doi.org/10.1016/j.tiv.2019.06.010
Liu Y, Chen S, Xue R et al (2016) Mefloquine effectively targets gastric cancer cells through phosphatase-dependent inhibition of PI3K/Akt/mTOR signaling pathway. Biochem Biophys Res Commun 470(2):350–355. https://doi.org/10.1016/j.bbrc.2016.01.046
Zhang S, Zuo L, Gui S et al (2012) Induction of cell differentiation and promotion of endocan gene expression in stomach cancer by melatonin. Mol Biol Rep 39(3):2843–2849. https://doi.org/10.1007/s11033-011-1043-4
Zhang S, Qi Y, Zhang H et al (2013) Melatonin inhibits cell growth and migration, but promotes apoptosis in gastric cancer cell line, SGC7901. Biotech Histochem 88(6):281–289. https://doi.org/10.3109/10520295.2013.769633
Li W, Fan M, Chen Y et al (2015) Melatonin induces cell apoptosis in AGS cells through the activation of JNK and P38 MAPK and the suppression of nuclear factor-kappa B: a novel therapeutic implication for gastric cancer. Cell Physiol Biochem 37(6):2323–2338. https://doi.org/10.1159/000438587
Wu SM, Lin WY, Shen CC et al (2016) Melatonin set out to ER stress signaling thwarts epithelial mesenchymal transition and peritoneal dissemination via calpain-mediated C/EBPbeta and NFkappaB cleavage. J Pineal Res 60(2):142–154. https://doi.org/10.1111/jpi.12295
Wang RX, Liu H, Xu L et al (2016) Melatonin downregulates nuclear receptor RZR/RORgamma expression causing growth-inhibitory and anti-angiogenesis activity in human gastric cancer cells in vitro and in vivo. Oncol Lett 12(2):897–903. https://doi.org/10.3892/ol.2016.4729
Li W, Wang Z, Chen Y et al (2017) Melatonin treatment induces apoptosis through regulating the nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells. Oncol Lett 13(4):2737–2744. https://doi.org/10.3892/ol.2017.5785
Wang X, Wang B, Xie J et al (2018) Melatonin inhibits epithelial to mesenchymal transition in gastric cancer cells via attenuation of IL1 beta/NFkappaB/MMP2/MMP9 signaling. Int J Mol Med 42(4):2221–2228. https://doi.org/10.3892/ijmm.2018.3788
Wei X, Qi Y, Jia N et al (2018) Hyperbaric oxygen treatment sensitizes gastric cancer cells to melatonin-induced apoptosis through multiple pathways. J Cell Biochem 119(8):6723–6731. https://doi.org/10.1002/jcb.26864
Zhu C, Huang Q, Zhu H (2018) Melatonin inhibits the proliferation of gastric cancer cells through regulating the miR-16-5p-Smad3 pathway. DNA Cell Biol 37(3):244–252. https://doi.org/10.1089/dna.2017.4040
Song J, Ma SJ, Luo JH et al (2018) Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway. Oncol Rep 39(4):1975–1983. https://doi.org/10.3892/or.2018.6282
Zheng Y, Tu J, Wang X et al (2019) The therapeutic effect of melatonin on GC by inducing cell apoptosis and autophagy induced by endoplasmic reticulum stress. Onco Targets Ther 12:10187–10198. https://doi.org/10.2147/OTT.S226140
Wei X, Chen S, Xu Z et al (2019) Melatonin inhibits the migration of human gastric carcinoma cells at least in part by remodeling tight junction. J Cell Biochem 120(6):9781–9786. https://doi.org/10.1002/jcb.28258
Song J, Ma SJ, Luo JH et al (2019) Downregulation of AKT and MDM2, melatonin induces apoptosis in AGS and MGC803 cells. Anat Rec (Hoboken) 302(9):1544–1551. https://doi.org/10.1002/ar.24101
Wang X, Wang B, Zhan W et al (2019) Melatonin inhibits lung metastasis of gastric cancer in vivo. Biomed Pharmacother 117:109018. https://doi.org/10.1016/j.biopha.2019.109018
Wang R, Liu H, Song J et al (2021) Activity of melatonin against gastric cancer growth in a chick embryo tumor xenograft model. Cancer Manag Res 13:8803–8808. https://doi.org/10.2147/CMAR.S329728
Huang Y, Yuan K, Tang M et al (2021) Melatonin inhibiting the survival of human gastric cancer cells under ER stress involving autophagy and Ras-Raf-MAPK signalling. J Cell Mol Med 25(3):1480–1492. https://doi.org/10.1111/jcmm.16237
Liu D, Shi K, Fu M et al (2021) Melatonin indirectly decreases gastric cancer cell proliferation and invasion via effects on cancer-associated fibroblasts. Life Sci 277:119497. https://doi.org/10.1016/j.lfs.2021.119497
Li W, Hu C, Zhong X et al (2022) Melatonin induces AGS gastric cancer cell apoptosis via regulating PERK/eIF2alpha and HSF1/NF-kappaB signaling pathway. Ann Clin Lab Sci 52(1):40–47
Lissoni P, Barni S, Tancini G et al (1993) Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract. Br J Cancer 67(6):1404–1407. https://doi.org/10.1038/bjc.1993.260
Lissoni P, Brivio F, Ardizzoia A et al (1993) Subcutaneous therapy with low-dose interleukin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Tumori 79(6):401–404
Lissoni P (2007) Biochemotherapy with standard chemotherapies plus the pineal hormone melatonin in the treatment of advanced solid neoplasms. Pathol Biol (Paris) 55(3–4):201–204. https://doi.org/10.1016/j.patbio.2006.12.025
Kato K, Gong J, Iwama H et al (2012) The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther 11(3):549–560. https://doi.org/10.1158/1535-7163.MCT-11-0594
Fang W, Cui H, Yu D et al (2014) Increased expression of phospho-acetyl-CoA carboxylase protein is an independent prognostic factor for human gastric cancer without lymph node metastasis. Med Oncol 31(7):15. https://doi.org/10.1007/s12032-014-0015-7
Lesan V, Ghaffari SH, Salaramoli J et al (2014) Evaluation of antagonistic effects of metformin with Cisplatin in gastric cancer cells. Int J Hematol Oncol Stem Cell Res 8(3):12–19
Chen G, Feng W, Zhang S et al (2015) Metformin inhibits gastric cancer via the inhibition of HIF1alpha/PKM2 signaling. Am J Cancer Res 5(4):1423–1434
Yu G, Fang W, Xia T et al (2015) Metformin potentiates rapamycin and cisplatin in gastric cancer in mice. Oncotarget 6(14):12748–12762. https://doi.org/10.18632/oncotarget.3327
Han G, Gong H, Wang Y et al (2015) AMPK/mTOR-mediated inhibition of survivin partly contributes to metformin-induced apoptosis in human gastric cancer cell. Cancer Biol Ther 16(1):77–87. https://doi.org/10.4161/15384047.2014.987021
Huang D, He X, Zou J et al (2016) Negative regulation of Bmi-1 by AMPK and implication in cancer progression. Oncotarget 7(5):6188–6200. https://doi.org/10.18632/oncotarget.6748
Courtois S, Duran RV, Giraud J et al (2017) Metformin targets gastric cancer stem cells. Eur J Cancer 84:193–201. https://doi.org/10.1016/j.ejca.2017.07.020
Song Z, Wei B, Lu C et al (2017) Metformin suppresses the expression of Sonic hedgehog in gastric cancer cells. Mol Med Rep 15(4):1909–1915. https://doi.org/10.3892/mmr.2017.6205
Zhuang S, Jian Y, Sun Y (2017) Metformin inhibits N-Methyl-N-nitrosourea induced gastric tumorigenesis in db/db mice. Exp Clin Endocrinol Diabetes 125(6):392–399. https://doi.org/10.1055/s-0043-100118
Wu X (2017) Effect of metformin combined with chemotherapeutic agents on gastric cancer cell line AGS. Pak J Pharm Sci 30(5(Special)):1833–1836
Valaee S, Yaghoobi MM, Shamsara M (2017) Metformin inhibits gastric cancer cells metastatic traits through suppression of epithelial-mesenchymal transition in a glucose-independent manner. PLoS One 12(3):e0174486. https://doi.org/10.1371/journal.pone.0174486
Li W, Wong CC, Zhang X et al (2018) CAB39L elicited an anti-Warburg effect via a LKB1-AMPK-PGC1alpha axis to inhibit gastric tumorigenesis. Oncogene 37(50):6383–6398. https://doi.org/10.1038/s41388-018-0402-1
Sekino N, Kano M, Matsumoto Y et al (2018) The antitumor effects of metformin on gastric cancer in vitro and on peritoneal metastasis. Anticancer Res 38(11):6263–6269. https://doi.org/10.21873/anticanres.12982
Tseng HH, Chen YZ, Chou NH et al (2021) Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis. Mol Ther Oncol 22:180–194. https://doi.org/10.1016/j.omto.2021.08.006
Bae WJ, Ahn JM, Byeon HE et al (2019) PTPRD-inactivation-induced CXCL8 promotes angiogenesis and metastasis in gastric cancer and is inhibited by metformin. J Exp Clin Cancer Res 38(1):484. https://doi.org/10.1186/s13046-019-1469-4
Lu CC, Chiang JH, Tsai FJ et al (2019) Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling. Int J Oncol 54(4):1271–1281. https://doi.org/10.3892/ijo.2019.4704
Li P, Tong L, Song Y et al (2019) Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion. J Cell Physiol 234(4):4515–4527. https://doi.org/10.1002/jcp.27269
Chen G, Yu C, Tang Z et al (2019) Metformin suppresses gastric cancer progression through calmodulin-like protein 3 secreted from tumor-associated fibroblasts. Oncol Rep 41(1):405–414. https://doi.org/10.3892/or.2018.6783
Chen Y, Gong W, Zhou Y et al (2020) Metformin up-regulated miR-107 expression and enhanced the inhibitory effect of miR-107 on gastric cancer growth. Transl Cancer Res 9(4):2941–2950. https://doi.org/10.21037/tcr.2020.03.25
Liu S, Yue C, Chen H et al (2020) Metformin promotes beclin1-dependent autophagy to inhibit the progression of gastric cancer. Onco Targets Ther 13:4445–4455. https://doi.org/10.2147/OTT.S242298
Miao ZF, Adkins-Threats M, Burclaff JR et al (2020) A metformin-responsive metabolic pathway controls distinct steps in gastric progenitor fate decisions and maturation. Cell Stem Cell 26(6):910–25.e6. https://doi.org/10.1016/j.stem.2020.03.006
Valaee S, Shamsara M, Yaghoobi MM (2021) Metformin is a novel suppressor for vimentin in human gastric cancer cell line. Int J Mol Cell Med 10(3):200–206. https://doi.org/10.22088/IJMCM.BUMS.10.3.200
Wang WH, Chen SK, Huang HC et al (2021) Proteomic analysis reveals that metformin suppresses PSMD2, STIP1, and CAP1 for preventing gastric cancer AGS cell proliferation and migration. ACS Omega 6(22):14208–14219. https://doi.org/10.1021/acsomega.1c00894
Zou J, Li C, Jiang S et al (2021) AMPK inhibits Smad3-mediated autoinduction of TGF-beta1 in gastric cancer cells. J Cell Mol Med 25(6):2806–2815. https://doi.org/10.1111/jcmm.16308
Fatehi-Agdam M, Vatankhah MA, Panahizadeh R et al (2021) Efficacy of metformin and chemotherapeutic agents on the inhibition of colony formation and Shh/Gli1 pathway: metformin/docetaxel versus metformin/5-fluorouracil. Drug Res (Stuttg) 71(1):17–25. https://doi.org/10.1055/a-1248-9008
Deng T, Shen P, Li A et al (2021) CCDC65 as a new potential tumor suppressor induced by metformin inhibits activation of AKT1 via ubiquitination of ENO1 in gastric cancer. Theranostics 11(16):8112–8128. https://doi.org/10.7150/thno.54961
Wang J, Huang Q, Hu X et al (2022) Disrupting circadian rhythm via the PER1-HK2 Axis reverses trastuzumab resistance in gastric cancer. Cancer Res 82(8):1503–1517. https://doi.org/10.1158/0008-5472.CAN-21-1820
Huang F, Xiang Y, Li T et al (2022) Metformin and MiR-365 synergistically promote the apoptosis of gastric cancer cells via MiR-365-PTEN-AMPK axis. Pathol Res Pract 230:153740. https://doi.org/10.1016/j.prp.2021.153740
Fujimoto S, Ohta M, Shrestha RD et al (1988) Enhancement of hyperthermochemotherapy for human gastric cancer in nude mice by thermosensitization with nitroimidazoles. Br J Cancer 58(1):42–45. https://doi.org/10.1038/bjc.1988.158
Skoropad VY, Berdov BA, Zagrebin VM (2003) Preoperative radiotherapy in combination with metronidazole for resectable gastric cancer: long-term results of a phase 2 study. Eur J Surg Oncol 29(2):166–170. https://doi.org/10.1053/ejso.2002.1324
Yu HE, Wang F, Yu F et al (2019) Suppression of fumarate hydratase activity increases the efficacy of cisplatin-mediated chemotherapy in gastric cancer. Cell Death Dis 10(6):413. https://doi.org/10.1038/s41419-019-1652-8
Li DQ, Pan LH, Shao ZM (2004) Inhibitory effects of mifepristone on the growth of human gastric cancer cell line MKN-45 in vitro and in vivo. Chin Med Sci J 19(4):237–242
Li DQ, Wang ZB, Bai J et al (2004) Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone. World J Gastroenterol 10(12):1722–1725. https://doi.org/10.3748/wjg.v10.i12.1722
Nakamura A, Matsunaga W, Gotoh A (2018) Autophagy induced by naftopidil inhibits apoptosis of human gastric cancer cells. Anticancer Res 38(2):803–809. https://doi.org/10.21873/anticanres.12287
Treese C, Hartl K, Potzsch M et al (2022) S100A4 is a strong negative prognostic marker and potential therapeutic target in adenocarcinoma of the stomach and esophagus. Cells 11(6). https://doi.org/10.3390/cells11061056
Baoping Y, Guoyong H, Jieping Y et al (2004) Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt/PKB activation in gastric cancer cell line. Dig Dis Sci 49(6):948–953. https://doi.org/10.1023/b:ddas.0000034553.58554.ab
Liu M, Luo XJ, Liao F et al (2011) Noscapine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo. Cancer Chemother Pharmacol 67(3):605–612. https://doi.org/10.1007/s00280-010-1356-3
Gao S, Yu BP, Li Y et al (2003) Antiproliferative effect of octreotide on gastric cancer cells mediated by inhibition of Akt/PKB and telomerase. World J Gastroenterol 9(10):2362–2365. https://doi.org/10.3748/wjg.v9.i10.2362
Wang CH, Tang CW, Liu CL et al (2003) Inhibitory effect of octreotide on gastric cancer growth via MAPK pathway. World J Gastroenterol 9(9):1904–1908. https://doi.org/10.3748/wjg.v9.i9.1904
Tang C, Liu C, Zhou X et al (2004) Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer. Int J Cancer 112(3):470–474. https://doi.org/10.1002/ijc.20256
Hu C, Yi C, Hao Z et al (2004) The effect of somatostatin and SSTR3 on proliferation and apoptosis of gastric cancer cells. Cancer Biol Ther 3(8):726–730. https://doi.org/10.4161/cbt.3.8.962
El-Salhy M (2005) Effects of octreotide, galanin and serotonin on a human gastric cancer cell line. Oncol Rep 13(5):787–791. https://doi.org/10.3892/or.13.5.787
Wang L, Huang X, Chai Y et al (2017) Octreotide inhibits the proliferation of gastric cancer cells through P300-HAT activity and the interaction of ZAC and P300. Oncol Rep 37(4):2041–2048. https://doi.org/10.3892/or.2017.5451
Feng S, Qiu G, Yang L et al (2021) Omeprazole improves chemosensitivity of gastric cancer cells by m6A demethylase FTO-mediated activation of mTORC1 and DDIT3 up-regulation. Biosci Rep 41(1). https://doi.org/10.1042/BSR20200842
Dowling S, Cox J, Cenedella RJ (2009) Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. Lipids 44(6):489–498. https://doi.org/10.1007/s11745-009-3298-2
Cao B, Deng H, Cui H et al (2021) Knockdown of PGM1 enhances anticancer effects of orlistat in gastric cancer under glucose deprivation. Cancer Cell Int 21(1):481. https://doi.org/10.1186/s12935-021-02193-3
Chen HY, Yang MD, Chou YC et al (2021) Ouabain Suppresses Cell Migration and Invasion in Human Gastric Cancer AGS Cells Through the Inhibition of MMP Signaling Pathways. Anticancer Res 41(9):4365–4375. https://doi.org/10.21873/anticanres.15241
Yeo M, Kim DK, Kim YB et al (2004) Selective induction of apoptosis with proton pump inhibitor in gastric cancer cells. Clin Cancer Res 10(24):8687–8696. https://doi.org/10.1158/1078-0432.CCR-04-1065
Huang S, Chen M, Ding X et al (2013) Proton pump inhibitor selectively suppresses proliferation and restores the chemosensitivity of gastric cancer cells by inhibiting STAT3 signaling pathway. Int Immunopharmacol 17(3):585–592. https://doi.org/10.1016/j.intimp.2013.07.021
Shen W, Zou X, Chen M et al (2013) Effect of pantoprazole on human gastric adenocarcinoma SGC7901 cells through regulation of phosphoLRP6 expression in Wnt/beta-catenin signaling. Oncol Rep 30(2):851–855. https://doi.org/10.3892/or.2013.2524
Shen Y, Chen M, Huang S et al (2016) Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2. Oncol Lett 11(1):717–722. https://doi.org/10.3892/ol.2015.3912
Feng S, Zheng Z, Feng L et al (2016) Proton pump inhibitor pantoprazole inhibits the proliferation, self-renewal and chemoresistance of gastric cancer stem cells via the EMT/betacatenin pathways. Oncol Rep 36(6):3207–3214. https://doi.org/10.3892/or.2016.5154
Koh JS, Joo MK, Park JJ et al (2018) Inhibition of STAT3 in gastric cancer: role of pantoprazole as SHP-1 inducer. Cell Biosci 8:50. https://doi.org/10.1186/s13578-018-0248-9
Zhang B, Ling T, Zhaxi P et al (2019) Proton pump inhibitor pantoprazole inhibits gastric cancer metastasis via suppression of telomerase reverse transcriptase gene expression. Cancer Lett 452:23–30. https://doi.org/10.1016/j.canlet.2019.03.029
Liu BH, Yuan TM, Huang CJ et al (2022) DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS. Am J Cancer Res 12(4):1465–1483
Wang Y, Lu JH, Wang F et al (2020) Inhibition of fatty acid catabolism augments the efficacy of oxaliplatin-based chemotherapy in gastrointestinal cancers. Cancer Lett 473:74–89. https://doi.org/10.1016/j.canlet.2019.12.036
Takahashi N, Okumura T, Motomura W et al (1999) Activation of PPARgamma inhibits cell growth and induces apoptosis in human gastric cancer cells. FEBS Lett 455(1–2):135–139. https://doi.org/10.1016/s0014-5793(99)00871-6
Konings IR, van der Gaast A, van der Wijk LJ et al (2010) The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer 46(18):3200–3204. https://doi.org/10.1016/j.ejca.2010.07.036
Peng Z, Zhang Y (2016) Propofol inhibits proliferation and accelerates apoptosis of human gastric cancer cells by regulation of microRNA-451 and MMP-2 expression. Genet Mol Res 15(2). https://doi.org/10.4238/gmr.15027078
Yang C, Gao J, Yan N et al (2017) Propofol inhibits the growth and survival of gastric cancer cells in vitro through the upregulation of ING3. Oncol Rep 37(1):587–593. https://doi.org/10.3892/or.2016.5218
Liu F, Qiu F, Fu M et al (2020) Propofol reduces epithelial to mesenchymal transition, invasion and migration of gastric cancer cells through the MicroRNA-195-5p/snail axis. Med Sci Monit 26:e920981. https://doi.org/10.12659/MSM.920981
Sui H, Zhu C, Li Z et al (2020) Propofol suppresses gastric cancer tumorigenesis by modulating the circular RNAPVT1/miR1955p/E26 oncogene homolog 1 axis. Oncol Rep 44(4):1736–1746. https://doi.org/10.3892/or.2020.7725
Zhang YF, Li CS, Zhou Y et al (2020) Propofol facilitates cisplatin sensitivity via lncRNA MALAT1/miR-30e/ATG5 axis through suppressing autophagy in gastric cancer. Life Sci 244:117280. https://doi.org/10.1016/j.lfs.2020.117280
Liu YP, Qiu ZZ, Li XH et al (2021) Propofol induces ferroptosis and inhibits malignant phenotypes of gastric cancer cells by regulating miR-125b-5p/STAT3 axis. World J Gastrointest Oncol 13(12):2114–2128. https://doi.org/10.4251/wjgo.v13.i12.2114
Bai ZM, Li XF, Yang Y et al (2021) Propofol inhibited gastric cancer proliferation via the hsa-miR-328-3p/STAT3 pathway. Clin Transl Oncol 23(9):1866–1873. https://doi.org/10.1007/s12094-021-02595-9
Liu L, Dong T, Sheng J (2021) Propofol suppresses gastric cancer progression by regulating circPDSS1/miR-1324/SOX4 Axis. Cancer Manag Res 13:6031–6043. https://doi.org/10.2147/CMAR.S312989
Cao Y, Fan L, Li L et al (2022) Propofol suppresses cell proliferation in gastric cancer cells through NRF2-mediated polyol pathway. Clin Exp Pharmacol Physiol 49(2):264–274. https://doi.org/10.1111/1440-1681.13595
Liao X, Che X, Zhao W et al (2010) The beta-adrenoceptor antagonist, propranolol, induces human gastric cancer cell apoptosis and cell cycle arrest via inhibiting nuclear factor kappaB signaling. Oncol Rep 24(6):1669–1676. https://doi.org/10.3892/or_00001032
Liao X, Che X, Zhao W et al (2010) Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro. Radiat Oncol 5:98. https://doi.org/10.1186/1748-717X-5-98
Liao X, Chaudhary P, Qiu G et al (2018) The role of propranolol as a radiosensitizer in gastric cancer treatment. Drug Des Devel Ther 12:639–645. https://doi.org/10.2147/DDDT.S160865
Hu Q, Liao P, Li W et al (2021) Clinical use of propranolol reduces biomarkers of proliferation in gastric cancer. Front Oncol 11:628613. https://doi.org/10.3389/fonc.2021.628613
Koh M, Takahashi T, Kurokawa Y et al (2021) Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis. Gastric Cancer 24(5):1037–1049. https://doi.org/10.1007/s10120-021-01184-7
Gu M, Zhang Y, Zhou X et al (2014) Rabeprazole exhibits antiproliferative effects on human gastric cancer cell lines. Oncol Lett 8(4):1739–1744. https://doi.org/10.3892/ol.2014.2354
Primrose JN, Miller GV, Preston SR et al (1998) A prospective randomised controlled study of the use of ranitidine in patients with gastric cancer. Yorkshire GI Tumour Group. Gut 42(1):17–19. https://doi.org/10.1136/gut.42.1.17
Chen VC, Hsu TC, Lin CF et al (2022) Association of risperidone with gastric cancer: triangulation method from cell study, animal study, and cohort study. Front Pharmacol 13:846455. https://doi.org/10.3389/fphar.2022.846455
Leung WK, Bai AH, Chan VY et al (2004) Effect of peroxisome proliferator activated receptor gamma ligands on growth and gene expression profiles of gastric cancer cells. Gut 53(3):331–338. https://doi.org/10.1136/gut.2003.021105
Chen BL, Yu J, Zeng ZR et al (2008) Rosiglitazone suppresses gastric carcinogenesis by up-regulating HCaRG expression. Oncol Rep 20(5):1093–1097. https://doi.org/10.3892/or_00000114
Zhang L, Hu JF, Li GQ et al (2012) Rosiglitazone reverses mitomycin C resistance in human gastric cancer cells. Am J Med Sci 343(5):382–387. https://doi.org/10.1097/MAJ.0b013e31822f3c63
Chen FZ, Mo XM, Wang QP et al (2013) Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice. Oncol Rep 30(6):2705–2712. https://doi.org/10.3892/or.2013.2704
Chen QY, Huang XB, Zhao YJ et al (2022) The peroxisome proliferator-activated receptor agonist rosiglitazone specifically represses tumour metastatic potential in chromatin inaccessibility-mediated FABP4-deficient gastric cancer. Theranostics 12(4):1904–1920. https://doi.org/10.7150/thno.66814
Manu KA, Shanmugam MK, Li F et al (2014) Simvastatin sensitizes human gastric cancer xenograft in nude mice to capecitabine by suppressing nuclear factor-kappa B-regulated gene products. J Mol Med 92(3):267–276. https://doi.org/10.1007/s00109-013-1095-0
Liu Q, Xia H, Zhou S et al (2020) Simvastatin Inhibits the malignant behaviors of gastric cancer cells by simultaneously suppressing YAP and beta-catenin signaling. Onco Targets Ther 13:2057–2066. https://doi.org/10.2147/OTT.S237693
Ortiz N, Diaz C (2020) Mevalonate pathway as a novel target for the treatment of metastatic gastric cancer. Oncol Lett 20(6):320. https://doi.org/10.3892/ol.2020.12183
Ortiz N, Delgado-Carazo JC, Diaz C (2021) Importance of mevalonate pathway lipids on the growth and survival of primary and metastatic gastric carcinoma cells. Clin Exp Gastroenterol 14:217–228. https://doi.org/10.2147/CEG.S310235
Xia Y, Jin Y, Cui D et al (2022) Antitumor effect of simvastatin in combination with DNA methyltransferase inhibitor on gastric cancer via GSDME-mediated pyroptosis. Front Pharmacol 13:860546. https://doi.org/10.3389/fphar.2022.860546
Kim ST, Kang JH, Lee J et al (2014) Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer 50(16):2822–2830. https://doi.org/10.1016/j.ejca.2014.08.005
Lang SA, Gaumann A, Koehl GE et al (2007) Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model. Int J Cancer 120(8):1803–1810. https://doi.org/10.1002/ijc.22442
Kamata S, Kishimoto T, Kobayashi S et al (2007) Possible involvement of persistent activity of the mammalian target of rapamycin pathway in the cisplatin resistance of AFP-producing gastric cancer cells. Cancer Biol Ther 6(7):1036–1043. https://doi.org/10.4161/cbt.6.7.4253
Shigematsu H, Yoshida K, Sanada Y et al (2010) Rapamycin enhances chemotherapy-induced cytotoxicity by inhibiting the expressions of TS and ERK in gastric cancer cells. Int J Cancer 126(11):2716–2725. https://doi.org/10.1002/ijc.24990
Kubota E, Kataoka H, Tanaka M et al (2011) ERas enhances resistance to CPT-11 in gastric cancer. Anticancer Res 31(10):3353–3360
Yao C, Liu J, Shao L (2011) Rapamycin inhibits the proliferation and apoptosis of gastric cancer cells by down regulating the expression of survivin. Hepato-Gastroenterology 58(107-108):1075–1080
Chen G, Chen SM, Wang X et al (2012) Inhibition of chemokine (CXC motif) ligand 12/chemokine (CXC motif) receptor 4 axis (CXCL12/CXCR4)-mediated cell migration by targeting mammalian target of rapamycin (mTOR) pathway in human gastric carcinoma cells. J Biol Chem 287(15):12132–12141. https://doi.org/10.1074/jbc.M111.302299
Chen W, Zou P, Zhao Z et al (2016) Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer. Redox Biol 10:78–89. https://doi.org/10.1016/j.redox.2016.09.006
Zhu CH, Peng SQ, Cui LL et al (2022) Synergistic effects of Rapamycin and Fluorouracil to treat a gastric tumor in a PTEN conditional deletion mouse model. Gastric Cancer 25(1):96–106. https://doi.org/10.1007/s10120-021-01229-x
Wang Q, Lu P, Wang T et al (2020) Sitagliptin affects gastric cancer cells proliferation by suppressing Melanoma-associated antigen-A3 expression through Yes-associated protein inactivation. Cancer Med 9(11):3816–3828. https://doi.org/10.1002/cam4.3024
Wang SF, Chen MS, Chou YC et al (2016) Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2alpha-ATF4-xCT pathway. Oncotarget 7(45):74132–74151. https://doi.org/10.18632/oncotarget.12356
Miyoshi S, Tsugawa H, Matsuzaki J et al (2018) Inhibiting xCT improves 5-fluorouracil resistance of gastric cancer induced by CD44 variant 9 expression. Anticancer Res 38(11):6163–6170. https://doi.org/10.21873/anticanres.12969
Takizawa K, Muramatsu K, Maruyama K et al (2020) Metabolic profiling of human gastric cancer cells treated with salazosulfapyridine. Technol Cancer Res Treat 19:1533033820928621. https://doi.org/10.1177/1533033820928621
Zhuang J, Liu X, Yang Y et al (2021) Sulfasalazine, a potent suppressor of gastric cancer proliferation and metastasis by inhibition of xCT: conventional drug in new use. J Cell Mol Med 25(12):5372–5380. https://doi.org/10.1111/jcmm.16548
Shitara K, Doi T, Nagano O et al (2017) Dose-escalation study for the targeting of CD44v(+) cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205). Gastric Cancer 20(2):341–349. https://doi.org/10.1007/s10120-016-0610-8
Shitara K, Doi T, Nagano O et al (2017) Phase 1 study of sulfasalazine and cisplatin for patients with CD44v-positive gastric cancer refractory to cisplatin (EPOC1407). Gastric Cancer 20(6):1004–1009. https://doi.org/10.1007/s10120-017-0720-y
Mu C, Peng RK, Guo CL et al (2021) Discovery of sertraline and its derivatives able to combat drug-resistant gastric cancer cell via inducing apoptosis. Bioorg Med Chem Lett 41:127997. https://doi.org/10.1016/j.bmcl.2021.127997
Wu YL, Sun B, Zhang XJ et al (2001) Growth inhibition and apoptosis induction of Sulindac on Human gastric cancer cells. World J Gastroenterol 7(6):796–800. https://doi.org/10.3748/wjg.v7.i6.796
Ma L, Xie YL, Yu Y et al (2005) Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac. World J Gastroenterol 11(12):1829–1832. https://doi.org/10.3748/wjg.v11.i12.1829
Sukumaran S, Patel HJ, Patel BM (2016) Evaluation of role of telmisartan in combination with 5-fluorouracil in gastric cancer cachexia. Life Sci 154:15–23. https://doi.org/10.1016/j.lfs.2016.04.029
Fujita N, Fujita K, Iwama H et al (2020) Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo. Oncol Rep 44(1):339–348. https://doi.org/10.3892/or.2020.7607
Tsujiya Y, Yamamori M, Hasegawa AI et al (2021) Telmisartan exerts cytotoxicity in scirrhous gastric cancer cells by inducing G0/G1 cell cycle arrest. Anticancer Res 41(11):5461–5468. https://doi.org/10.21873/anticanres.15358
Mu J, Xu H, Yang Y et al (2014) Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer. Oncol Rep 31(5):2107–2114. https://doi.org/10.3892/or.2014.3068
Yashiro M, Chung YS, Sowa M (1997) Tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid) down-regulates the growth of scirrhous gastric cancer. Anticancer Res 17(2A):895–900
Murahashi K, Yashiro M, Inoue T et al (1998) Tranilast and cisplatin as an experimental combination therapy for scirrhous gastric cancer. Int J Oncol 13(6):1235–1240. https://doi.org/10.3892/ijo.13.6.1235
Yashiro M, Murahashi K, Matsuoka T et al (2003) Tranilast (N-3,4-dimethoxycinamoyl anthranilic acid): a novel inhibitor of invasion-stimulating interaction between gastric cancer cells and orthotopic fibroblasts. Anticancer Res 23(5A):3899–3904
Nakajima K, Okita Y, Matsuda S (2004) Sensitivity of scirrhous gastric cancer to 5-fluorouracil and the role of cancer cell-stromal fibroblast interaction. Oncol Rep 12(1):85–90
Laurino S, Mazzone P, Ruggieri V et al (2021) Cationic channel TRPV2 overexpression promotes resistance to cisplatin-induced apoptosis in gastric cancer cells. Front Pharmacol 12:746628. https://doi.org/10.3389/fphar.2021.746628
Wang J, Chen X, Su L et al (2016) Suppressive effects on cell proliferation and motility in gastric cancer SGC-7901 cells by introducing ulinastatin in vitro. Anti-Cancer Drugs 27(7):651–659. https://doi.org/10.1097/CAD.0000000000000378
Lim SC, Duong HQ, Choi JE et al (2011) Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells. Carcinogenesis 32(5):723–731. https://doi.org/10.1093/carcin/bgr038
Lim SC, Han SI (2015) Ursodeoxycholic acid effectively kills drug-resistant gastric cancer cells through induction of autophagic death. Oncol Rep 34(3):1261–1268. https://doi.org/10.3892/or.2015.4076
Yagi Y, Fushida S, Harada S et al (2010) Effects of valproic acid on the cell cycle and apoptosis through acetylation of histone and tubulin in a scirrhous gastric cancer cell line. J Exp Clin Cancer Res 29:149. https://doi.org/10.1186/1756-9966-29-149
Sun J, Piao J, Li N et al (2020) Valproic acid targets HDAC1/2 and HDAC1/PTEN/Akt signalling to inhibit cell proliferation via the induction of autophagy in gastric cancer. FEBS J 287(10):2118–2133. https://doi.org/10.1111/febs.15122
Amnekar RV, Khan SA, Rashid M et al (2020) Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer. World J Gastroenterol 26(6):598–613. https://doi.org/10.3748/wjg.v26.i6.598
Jahani M, Khanahmad H, Nikpour P (2021) Evaluation of the effects of valproic acid treatment on cell survival and epithelial-mesenchymal transition-related features of human gastric cancer cells. J Gastrointest Cancer 52(2):676–681. https://doi.org/10.1007/s12029-019-00332-8
Fushida S, Kinoshita J, Kaji M et al (2016) Paclitaxel plus valproic acid versus paclitaxel alone as second- or third-line therapy for advanced gastric cancer: a randomized Phase II trial. Drug Des Devel Ther 10:2353–2358. https://doi.org/10.2147/DDDT.S110425
Shchepotin IB, Shabahang M, Nauta RJ et al (1994) Antitumour activity of 5-fluorouracil, verapamil and hyperthermia against human gastric adenocarcinoma cell (AGS) in vitro. Surg Oncol 3(5):287–294. https://doi.org/10.1016/0960-7404(94)90031-0
Shchepotin IB, Buras RR, Nauta RJ et al (1994) Effect of mitomycin C, verapamil, and hyperthermia on human gastric adenocarcinoma. Cancer Chemother Pharmacol 34(3):257–260. https://doi.org/10.1007/BF00685086
Nozue M, Nishida M, Todoroki T et al (1995) Selection of three out of 24 anti-cancer agents in poorly-differentiated gastric cancer cell lines, evaluated by the AUC/delta IC50 ratio. Anti-Cancer Drugs 6(2):291–302. https://doi.org/10.1097/00001813-199504000-00014
Wang X, Li Y, Fan GF et al (2020) Effect of verapamil in the reversal of doxorubicin chemotherapy resistance in advanced gastric cancer. Eur Rev Med Pharmacol Sci 24(14):7753–7763. https://doi.org/10.26355/eurrev_202007_22278
Ning Z, Chen D, Liu A et al (2014) Efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer. Cell Biochem Biophys 68(1):195–200. https://doi.org/10.1007/s12013-013-9689-2
Kang MH, Jeong GS, Smoot DT et al (2017) Verteporfin inhibits gastric cancer cell growth by suppressing adhesion molecule FAT1. Oncotarget 8(58):98887–98897. https://doi.org/10.18632/oncotarget.21946
Xiong J, Wang S, Chen T et al (2019) Verteporfin blocks Clusterin which is required for survival of gastric cancer stem cell by modulating HSP90 function. Int J Biol Sci 15(2):312–324. https://doi.org/10.7150/ijbs.29135
Giraud J, Molina-Castro S, Seeneevassen L et al (2020) Verteporfin targeting YAP1/TAZ-TEAD transcriptional activity inhibits the tumorigenic properties of gastric cancer stem cells. Int J Cancer 146(8):2255–2267. https://doi.org/10.1002/ijc.32667
Hasegawa T, Sugihara T, Hoshino Y et al (2021) Photosensitizer verteporfin inhibits the growth of YAP- and TAZ-dominant gastric cancer cells by suppressing the anti-apoptotic protein Survivin in a light-independent manner. Oncol Lett 22(4):703. https://doi.org/10.3892/ol.2021.12964
Zheng QS, Sun XL, Wang CH (2002) Redifferentiation of human gastric cancer cells induced by ascorbic acid and sodium selenite. Biomed Environ Sci 15(3):223–232
Oliveira CP, Kassab P, Lopasso FP et al (2003) Protective effect of ascorbic acid in experimental gastric cancer: reduction of oxidative stress. World J Gastroenterol 9(3):446–448. https://doi.org/10.3748/wjg.v9.i3.446
Sun YX, Zheng QS, Li G et al (2006) Mechanism of ascorbic acid-induced reversion against malignant phenotype in human gastric cancer cells. Biomed Environ Sci 19(5):385–391
Ha YM, Park MK, Kim HJ et al (2009) High concentrations of ascorbic acid induces apoptosis of human gastric cancer cell by p38-MAP kinase-dependent up-regulation of transferrin receptor. Cancer Lett 277(1):48–54. https://doi.org/10.1016/j.canlet.2008.11.020
Nagappan A, Park KI, Park HS et al (2012) Vitamin C induces apoptosis in AGS cells by down-regulation of 14-3-3sigma via a mitochondrial dependent pathway. Food Chem 135(3):1920–1928. https://doi.org/10.1016/j.foodchem.2012.06.050
Lu YX, Wu QN, Chen DL et al (2018) Pharmacological ascorbate suppresses growth of gastric cancer cells with GLUT1 overexpression and enhances the efficacy of oxaliplatin through redox modulation. Theranostics 8(5):1312–1326. https://doi.org/10.7150/thno.21745
O’Leary BR, Houwen FK, Johnson CL et al (2018) Pharmacological ascorbate as an adjuvant for enhancing radiation-chemotherapy responses in gastric adenocarcinoma. Radiat Res 189(5):456–465. https://doi.org/10.1667/RR14978.1
Ghavami G, Sardari S (2020) Synergistic effect of vitamin C with cisplatin for inhibiting proliferation of gastric cancer cells. Iran Biomed J 24(2):119–127
Chen D, Wei X, Yang K et al (2022) Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS-STAT3 pathway. J Int Med Res 50(4):3000605221093308. https://doi.org/10.1177/03000605221093308
Wang GQ, Dawsey SM, Li JY et al (1994) Effects of vitamin/mineral supplementation on the prevalence of histological dysplasia and early cancer of the esophagus and stomach: results from the General Population Trial in Linxian, China. Cancer Epidemiol Biomarkers Prev 3(2):161–166
Tsubono Y, Okubo S, Hayashi M et al (1997) A randomized controlled trial for chemoprevention of gastric cancer in high-risk Japanese population; study design, feasibility and protocol modification. Jpn J Cancer Res 88(4):344–349. https://doi.org/10.1111/j.1349-7006.1997.tb00387.x
Wang F, He MM, Wang ZX et al (2019) Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. BMC Cancer 19(1):460. https://doi.org/10.1186/s12885-019-5696-z
Baek S, Lee YS, Shim HE et al (2011) Vitamin D3 regulates cell viability in gastric cancer and cholangiocarcinoma. Anat Cell Biol 44(3):204–209. https://doi.org/10.5115/acb.2011.44.3.204
Park MR, Lee JH, Park MS et al (2012) Suppressive effect of 19-nor-1alpha-25-dihydroxyvitamin D2 on gastric cancer cells and peritoneal metastasis model. J Korean Med Sci 27(9):1037–1043. https://doi.org/10.3346/jkms.2012.27.9.1037
Bao A, Li Y, Tong Y et al (2013) Tumor-suppressive effects of 1, 25-dihydroxyvitamin D3 in gastric cancer cells. Hepato-Gastroenterology 60(124):943–948. https://doi.org/10.5754/hge121003
Bao A, Li Y, Tong Y et al (2014) 1,25-Dihydroxyvitamin D(3) and cisplatin synergistically induce apoptosis and cell cycle arrest in gastric cancer cells. Int J Mol Med 33(5):1177–1184. https://doi.org/10.3892/ijmm.2014.1664
Chang S, Gao L, Yang Y et al (2015) miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells. Oncotarget 6(10):7675–7685. https://doi.org/10.18632/oncotarget.3048
Li M, Li L, Zhang L et al (2017) 1,25-Dihydroxyvitamin D3 suppresses gastric cancer cell growth through VDR- and mutant p53-mediated induction of p21. Life Sci 179:88–97. https://doi.org/10.1016/j.lfs.2017.04.021
Wu J, Zhao Q, Zhao Y et al (2021) Dicer increases the indication for trastuzumab treatment in gastric cancer patients via overexpression of human epidermal growth factor receptor 2. Sci Rep 11(1):6993. https://doi.org/10.1038/s41598-021-86485-8
Urashima M, Ohdaira H, Akutsu T et al (2019) Effect of vitamin D supplementation on relapse-free survival among patients with digestive tract cancers: the AMATERASU randomized clinical trial. JAMA 321(14):1361–1369. https://doi.org/10.1001/jama.2019.2210
Lee MH, Cho Y, Kim DH et al (2016) Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1. Am J Transl Res 8(12):5246–5255
Bona AB, Calcagno DQ, Ribeiro HF et al (2020) Menadione reduces CDC25B expression and promotes tumor shrinkage in gastric cancer. Ther Adv Gastroenterol 13:1756284819895435. https://doi.org/10.1177/1756284819895435
Yasuda C, Kato M, Kuroda D et al (1997) Experimental studies on potentiation of the antitumor activity of 5-fluorouracil with 3′-azido-3′-deoxythymidine for the gastric cancer cell line MKN28 in vivo. Jpn J Cancer Res 88(1):97–102. https://doi.org/10.1111/j.1349-7006.1997.tb00307.x
Sun YQ, Guo TK, Xi YM et al (2007) Effects of AZT and RNA-protein complex (FA-2-b-beta) extracted from Liang Jin mushroom on apoptosis of gastric cancer cells. World J Gastroenterol 13(31):4185–4191. https://doi.org/10.3748/wjg.v13.i31.4185
Kim BJ, Kim SY, Lee S et al (2012) The role of transient receptor potential channel blockers in human gastric cancer cell viability. Can J Physiol Pharmacol 90(2):175–186. https://doi.org/10.1139/y11-114
Tang J, Zhang C, Lin J et al (2021) ALOX5-5-HETE promotes gastric cancer growth and alleviates chemotherapy toxicity via MEK/ERK activation. Cancer Med 10(15):5246–5255. https://doi.org/10.1002/cam4.4066
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Leite, M., Seruca, R., Gonçalves, J.M. (2023). Drug Repurposing in Gastric Cancer: Current Status and Future Perspectives. In: Corso, G., Veronesi, P., Roviello, F. (eds) Hereditary Gastric and Breast Cancer Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-031-21317-5_20
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