Abstract
Autophagy is an intracellular degradation pathway that delivers organelles or protein to the lysosome and has been recently implicated in the resistance of gastric cancer to chemotherapy. This study aimed to investigate whether blocking autophagy is a new approach for the treatment of chemoresistant gastric cancer. SGC-7901 gastric cancer cell line was treated with 5-fluorouracil (5-FU) or/and autophagy inhibitor bafilomycin A1. Cell viability and growth were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and clonogenic assay. Apoptosis was evaluated by flow cytometry. Cell migratory and invasive ability were evaluated by migration and invasion assays. Autophagy was evaluated by scanning electron microscopic, acridine orange staining, and Western blot analysis. We observed that 5-FU induced autophagy in SGC-7901 cells. Bafilomycin A1 decreased the viability and clone formation, inhibited the invasive and migratory ability, and increased the apoptosis of SGC-7901 cells. Taken together, our data suggest that chemotherapy-induced autophagy contributes to gastric cancer chemoresistance, and the inhibition of autophagy is a promising strategy for gastric cancer therapy.
Similar content being viewed by others
References
Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.
Bang YJ, Van Gutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (TOGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.
Mizushima N. The pleiotropic role of autophagy: from protein metabolism to bactericide. Cell Death Differ. 2005;12:1535–41.
Tsuchihara K, Fujii S, Esumi H. Autophagy and cancer: dynamism of the metabolism of tumor cells and tissues. Cancer Lett. 2009;278:130–8.
Ito H, Daido S, Kanzawa T, Kondo S, et al. Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells. Int J Oncol. 2005;26:1401–10.
Yu M, Gou WF, Zhao S, et al. Beclin 1 expression is an independent prognostic factor for gastric carcinomas. Tumour Biol. 2013;4:1071–83.
Xu L, Qu XJ, Liu YP, et al. Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells. Chin J Cancer. 2011;30:490–6.
Kawai A, Uchiyama H, Takano S, et al. Autophagosome-lysosome fusion depends on the pH in acidic compartments in CHO cells. Autophagy. 2007;3:154–7.
Wu S, Wang X, Chen J, Chen Y. Autophagy of cancer stem cells is involved with chemoresistance of colon cancer cells. Biochem Biophys Res Commun. 2013;434:898–903.
Greene LM, Nolan DP, Regan-Komito D, et al. Inhibition of late-stage autophagy synergistically enhances pyrrolo-1,5-benzoxazepine-6-induced apoptotic cell death in human colon cancer cells. Int J Oncol. 2013;43:927–35.
Michel V, Licon-Munoz Y, Trujillo K, et al. Inhibitors of vacuolar ATPase proton pumps inhibit human prostate cancer cell invasion and prostate-specific antigen expression and secretion. Int J Cancer. 2013;132:1–10.
Luo S, Rubinsztein DC. Apoptosis blocks beelin l-dependent autophagosome synthesis: an effect rescued by Bel-xL. Cell Death Differ. 2010;17:268–77.
Kim YS, Shin JH, Bae MK, et al. Autophagy activity in pulmonary metastatic tumor tissues from colorectal cancer: a pilot study. Yonsei Med J. 2014;55:1484–8.
Cui J, Hu YF, Feng XM, Tian T, Guo YH, Ma JW, et al. EGFR inhibitors and autophagy in cancer treatment. Tumour Biol. 2014;35:11701–9.
Pattingre S, Espert L, Biard-Piechaczyk M, Codogno P. Regulation of macroautophagy by mTOR and Beclin 1 complexes. Biochimie. 2008;90:313–23.
Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. 1999;402:672–6.
Moscat J, Diaz-Meco MT. p62 at the crossroads of autophagy, apoptosis and cancer. Cell. 2009;137:1001–4.
Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8:445–544.
Acknowledgments
This study was supported by the National Key Clinical Specialist Construction Programs of China.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, Lq., Xie, Wj., Pan, D. et al. Inhibition of autophagy by bafilomycin A1 promotes chemosensitivity of gastric cancer cells. Tumor Biol. 37, 653–659 (2016). https://doi.org/10.1007/s13277-015-3842-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-3842-z