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Resveratrol inhibits TGF-β1-induced EMT in gastric cancer cells through Hippo-YAP signaling pathway

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Abstract

Objective

To investigate the effects of resveratrol (RSVL) on epithelial-mesenchymal transition (EMT) and biological behaviors of gastric cancer cells.

Methods

SGC-7901 cells were treated with RSVL, followed by TGF-β1 treatment for induction of EMT. Cell proliferation was tested by MTT assay, migration and invasion by Transwell and scratch assays, and Hippo-YAP signaling pathway activation by immunofluorescence. The RNA and protein expressions of E-cadherin, Vimentin, N-cadherin, and Snail were detected by qPCR and Western blot. A tumor model was constructed to examine the effect of RSVL on gastric tumor growth.

Results

RSVL inhibited the migration, invasion, and growth of gastric cancer cells in concentration- and time-dependent manners. RSVL inhibited TGF-β1-induced EMT of gastric cancer cells, which might relate to inactivation of the Hippo-YAP pathway. In the mouse tumor model, RSVL inhibited the EMT process by suppressing the Hippo-YAP pathway.

Conclusion

RSVL inhibited EMT of gastric cancer cells probably by weakening the Hippo-YAP signaling pathway.

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References

  1. Ang TL, Fock KM. Clinical epidemiology of gastric cancer. Singapore Med J. 2014;55(12):621–8.

    Article  Google Scholar 

  2. Machlowska J, Baj J, Sitarz M, et al. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci. 2020;21(11):4012.

    Article  CAS  Google Scholar 

  3. Rau B, Brandl A, Thuss-Patience P, et al. The efficacy of treatment options for patients with gastric cancer and peritoneal metastasis. Gastric Cancer. 2019;22(6):1226–37.

    Article  CAS  Google Scholar 

  4. Lui SA, Tan WB, Tai BC, et al. Predictors of survival outcome following radical gastrectomy for gastric cancer. ANZ J Surg. 2019;89(1–2):84–9.

    Article  Google Scholar 

  5. Song Z, Wu Y, Yang J, et al. Progress in the treatment of advanced gastric cancer. Tumour Biol. 2017;39(7):1010428317714626.

    Article  Google Scholar 

  6. Peng Z, Wang CX, Fang EH, et al. Role of epithelial-mesenchymal transition in gastric cancer initiation and progression. World J Gastroenterol. 2014;20(18):5403–10.

    Article  CAS  Google Scholar 

  7. Kozak J, Forma A, Czeczelewski M, et al. Inhibition or reversal of the epithelial-mesenchymal transition in gastric cancer: pharmacological approaches. Int J Mol Sci. 2020;22(1):277.

    Article  Google Scholar 

  8. Xu J, Liu D, Niu H, et al. Resveratrol reverses Doxorubicin resistance by inhibiting epithelial-mesenchymal transition (EMT) through modulating PTEN/Akt signaling pathway in gastric cancer. J Exp Clin Cancer Res. 2017;36(1):19.

    Article  Google Scholar 

  9. Gao Q, Yuan Y, Gan HZ, et al. Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis. Oncol Lett. 2015;9(5):2381–7.

    Article  CAS  Google Scholar 

  10. Kim S, Kim W, Kim DH, et al. Resveratrol suppresses gastric cancer cell proliferation and survival through inhibition of PIM-1 kinase activity. Arch Biochem Biophys. 2020;689:108413.

    Article  CAS  Google Scholar 

  11. Xu QH, Xiao Y, Li XQ, et al. Resveratrol counteracts hypoxia-induced gastric cancer invasion and EMT through hedgehog pathway suppression. Anticancer Agents Med Chem. 2020;20(9):1105–14.

    Article  CAS  Google Scholar 

  12. Meng Z, Moroishi T, Guan KL. Mechanisms of Hippo pathway regulation. Genes Dev. 2016;30(1):1–17.

    Article  CAS  Google Scholar 

  13. Zheng M, Jacob J, Hung SH, et al. The Hippo pathway in cardiac regeneration and homeostasis: new perspectives for cell-free therapy in the injured heart. Biomolecules. 2020;10(7):1024.

    Article  Google Scholar 

  14. Gao Y, Li J, Xi H, et al. Stearoyl-CoA-desaturase-1 regulates gastric cancer stem-like properties and promotes tumour metastasis via Hippo/YAP pathway. Br J Cancer. 2020;122(12):1837–47.

    Article  CAS  Google Scholar 

  15. Zhou H, Li G, Huang S, et al. SOX9 promotes epithelial-mesenchymal transition via the Hippo-YAP signaling pathway in gastric carcinoma cells. Oncol Lett. 2019;18(1):599–608.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Xu G, Chen J, Wang G, et al. Resveratrol inhibits the tumorigenesis of follicular thyroid cancer via ST6GAL2-regulated activation of the Hippo signaling pathway. Mol Ther Oncolytics. 2020;16:124–33.

    Article  CAS  Google Scholar 

  17. Zong W, Yu C, Wang P, et al. Overexpression of SASH1 inhibits TGF-beta1-induced EMT in gastric cancer cells. Oncol Res. 2016;24(1):17–23.

    Article  Google Scholar 

  18. Burja B, Kuret T, Janko T, et al. Olive leaf extract attenuates inflammatory activation and DNA damage in human arterial endothelial cells. Front Cardiovasc Med. 2019;6:56.

    Article  CAS  Google Scholar 

  19. Odero-Marah V, Hawsawi O, Henderson V, et al. Epithelial-mesenchymal transition (EMT) and prostate cancer. Adv Exp Med Biol. 2018;1095:101–10.

    Article  CAS  Google Scholar 

  20. Li N, Feng Y, Hu Y, et al. Helicobacter pylori CagA promotes epithelial mesenchymal transition in gastric carcinogenesis via triggering oncogenic YAP pathway. J Exp Clin Cancer Res. 2018;37(1):280.

    Article  Google Scholar 

  21. Hong G, Yan Y, Zhong Y, et al. Combined ischemic preconditioning and resveratrol improved bloodbrain barrier breakdown via Hippo/YAP/TAZ signaling pathway. CNS Neurol Disord Drug Targets. 2019;18(9):713–22.

    Article  CAS  Google Scholar 

  22. Ko JH, Sethi G, Um JY, et al. The role of resveratrol in cancer therapy. Int J Mol Sci. 2017;18(12):2589.

    Article  Google Scholar 

  23. Zulueta A, Caretti A, Signorelli P, et al. Resveratrol: a potential challenger against gastric cancer. World J Gastroenterol. 2015;21(37):10636–43.

    Article  CAS  Google Scholar 

  24. Kim CW, Hwang KA, Choi KC. Anti-metastatic potential of resveratrol and its metabolites by the inhibition of epithelial-mesenchymal transition, migration, and invasion of malignant cancer cells. Phytomedicine. 2016;23(14):1787–96.

    Article  CAS  Google Scholar 

  25. He Z, Dong W, Li Q, et al. Sauchinone prevents TGF-beta-induced EMT and metastasis in gastric cancer cells. Biomed Pharmacother. 2018;101:355–61.

    Article  CAS  Google Scholar 

  26. Liu J, Chen Y, Cao Z, et al. Babao Dan inhibits the migration and invasion of gastric cancer cells by suppressing epithelial-mesenchymal transition through the TGF-beta/Smad pathway. J Int Med Res. 2020;48(6):300060520925598.

    Article  CAS  Google Scholar 

  27. Su B, Su J, Zeng Y, et al. Diallyl disulfide inhibits TGFbeta1induced upregulation of Rac1 and betacatenin in epithelialmesenchymal transition and tumor growth of gastric cancer. Oncol Rep. 2018;39(6):2797–806.

    CAS  PubMed  Google Scholar 

  28. Yang Z, Xie Q, Chen Z, et al. Resveratrol suppresses the invasion and migration of human gastric cancer cells via inhibition of MALAT1-mediated epithelial-to-mesenchymal transition. Exp Ther Med. 2019;17(3):1569–78.

    CAS  PubMed  Google Scholar 

  29. Han G, Xia J, Gao J, et al. Anti-tumor effects and cellular mechanisms of resveratrol. Drug Discov Ther. 2015;9(1):1–12.

    Article  CAS  Google Scholar 

  30. Xu J, Li N, Deng W, et al. Long noncoding RNA FER1L4 suppresses proliferation, invasion, migration and lymphatic metastasis of gastric cancer cells through inhibiting the Hippo-YAP signaling pathway. Am J Transl Res. 2020;12(9):5481–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Yan H, Qiu C, Sun W, et al. Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy. Oncol Rep. 2018;39(4):1671–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim YN, Choe SR, Cho KH, et al. Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis. Exp Mol Med. 2017;49(2): e296.

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge and appreciate Lianwu Zhao for his valuable comments on the article, Jiangxi Cancer Hospital for providing the experimental site, and Jun Zou, Meijian Wang, and Yongfeng Su for their support.

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Authors and Affiliations

  1. General Department of Oncology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, 330029, Jiangxi, People’s Republic of China

    Lei Deng, Yongfeng Su & Meijian Wang

  2. Department of Abdominal Tumor Surgery, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, 330029, Jiangxi, People’s Republic of China

    Jun Zou

  3. Department of Gastroenterology, Gaoxin Branch Of The First Affiliated Hospital Of Nanchang University, No. 7889 Changdong Ave, Gaoxin District, Nanchang, 330029, Jiangxi, People’s Republic of China

    Lianwu Zhao

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  1. Lei Deng
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  2. Jun Zou
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  4. Meijian Wang
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Correspondence to Lianwu Zhao.

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Ethical approval All procedures conformed to the regulations of the Animal Ethics Committee of Gaoxin hospital, the First Affiliated Hospital of Nanchang University.

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Deng, L., Zou, J., Su, Y. et al. Resveratrol inhibits TGF-β1-induced EMT in gastric cancer cells through Hippo-YAP signaling pathway. Clin Transl Oncol 24, 2210–2221 (2022). https://doi.org/10.1007/s12094-022-02882-z

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  • DOI: https://doi.org/10.1007/s12094-022-02882-z

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