Autophagy Inhibition Sensitizes Cisplatin Cytotoxicity in Human Gastric Cancer Cell Line Sgc7901

  • Zhang, Hui-Qing (The 3rd department of Medical Oncology, Jiangxi Provincial Tumor Hospital) ;
  • He, Bo (The 3rd department of Medical Oncology, Jiangxi Provincial Tumor Hospital) ;
  • Fang, Nian (Gastrointestinal Department of Internal Medicine, the 4th Affiliated Hospital of Nanchang University) ;
  • Lu, Shan (The 3rd department of Medical Oncology, Jiangxi Provincial Tumor Hospital) ;
  • Liao, Yu-Qian (The 3rd department of Medical Oncology, Jiangxi Provincial Tumor Hospital) ;
  • Wan, Yi-Ye (The 3rd department of Medical Oncology, Jiangxi Provincial Tumor Hospital)
  • Published : 2013.08.30


We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)-induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells were treated with DDP and/or chloroquine, cell proliferation was measured using MTT assay; cell apoptosis was determined by flow cytometry; autophagy and apotosis-related proteins expression were detected by Western blot; and quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP for 24 h, the rates of cell apoptosis were ($21.07{\pm}2.12$)%. Autophagy, characterized by an increase in the number of autophagic vesicles and the level of LC3-II protein was observed in cells treated with DDP. After inhibition of autophagy by chloroquine, the rates of cell apoptosis were increased to ($30.16{\pm}3.54$)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2 protein was decreased. Therefore, autophagy protects human gastric cancer cell line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote apoptosis, and combination therapy with DDP and chloroquine may be a promising therapeutic strategy for gastric cancer.


Autophagy;cisplatin;chloroquine;apoptosis;gastric cancer


  1. Ashford TP, Porter KR (1962). Cytoplasmic components in hepatic cell lysosomes. J Cell Biol, 12, 198-202.
  2. Bang YJ, Van Cutsem E, Feyereislova A, et al (2010). 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, randomised controlled trial. Lancet, 376, 687-97.
  3. Chen S, Rehman SK, Zhang W, et al (2010). Autophagy is a therapeutic target in anticancer drug resistance. Biochim Biophys Acta, 1806, 220-9.
  4. Cunningham D, Allum WH, Stenning SP, et al (2006). Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med, 355, 11-20.
  5. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  6. Kimura T, Takabatake Y, Takahashi A, et al (2013). Chloroquine in cancer therapy, a double-edged sword of autophagy. Cancer Res, 73, 3-7.
  7. Klionsky DJ (2008). Autophagy revisited, a conversation with Christian de Duve. Autophagy, 4, 740-3.
  8. Levine B, Klionsky DJ (2004). Development by self-digestion, molecular mechanisms and biological functions of autophagy. Dev Cell, 6, 463-77.
  9. Levine B, Kroemer G (2008). Autophagy in the pathogenesis of disease. Cell, 132, 27-42.
  10. Levy JM, Thorburn A (2011). Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacol Ther, 131, 130-41.
  11. Li Y, Zhang J, Ma H (2013). Protective role of autophagy in matrine induced gastric cancer cell death. Int J Oncol, 42, 1417-26
  12. Mathew R, Karantza-Wadsworth V, White E (2007). Role of autophagy in cancer. Nat Rev Cancer, 7, 961-7.
  13. Pasini F, Fraccon AP, DE Manzoni G (2011). The role of chemotherapy in metastatic gastric cancer. Anticancer Res, 31, 3543-54.
  14. Ren JH, He WS, Nong L, et al (2010). Acquired cisplatin resistance in human lung adenocarcinoma cells is associated with enhanced autophagy. Cancer Biother Radiopharm, 25, 75-80.
  15. Sotelo J, Briceno E, Lopez-Gonzalez MA (2006). Adding chloroquine to conventional treatment for glioblastoma multiforme, a randomized, double-blind, placebo-controlled trial. Ann Intern Med, 144, 337-43.
  16. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al (2006). Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer, a report of the V325 Study Group. J Clin Oncol, 24, 4991-7.
  17. White E (2012). Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer, 12, 401-10.

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