Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

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
Download PDF
⟨ Previous Next ⟩

Abstract

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.

Keywords

References

  1. Ashford TP, Porter KR (1962). Cytoplasmic components in hepatic cell lysosomes. J Cell Biol, 12, 198-202. https://doi.org/10.1083/jcb.12.1.198
  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. https://doi.org/10.1016/S0140-6736(10)61121-X
  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. https://doi.org/10.1056/NEJMoa055531
  5. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  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. https://doi.org/10.1158/0008-5472.CAN-12-2464
  7. Klionsky DJ (2008). Autophagy revisited, a conversation with Christian de Duve. Autophagy, 4, 740-3. https://doi.org/10.4161/auto.6398
  8. Levine B, Klionsky DJ (2004). Development by self-digestion, molecular mechanisms and biological functions of autophagy. Dev Cell, 6, 463-77. https://doi.org/10.1016/S1534-5807(04)00099-1
  9. Levine B, Kroemer G (2008). Autophagy in the pathogenesis of disease. Cell, 132, 27-42. https://doi.org/10.1016/j.cell.2007.12.018
  10. Levy JM, Thorburn A (2011). Targeting autophagy during cancer therapy to improve clinical outcomes. Pharmacol Ther, 131, 130-41. https://doi.org/10.1016/j.pharmthera.2011.03.009
  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. https://doi.org/10.1038/nrc2254
  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. https://doi.org/10.1089/cbr.2009.0701
  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. https://doi.org/10.7326/0003-4819-144-5-200603070-00008
  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. https://doi.org/10.1200/JCO.2006.06.8429
  17. White E (2012). Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer, 12, 401-10. https://doi.org/10.1038/nrc3262

Cited by

  1. Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis vol.15, pp.11, 2014, https://doi.org/10.7314/APJCP.2014.15.11.4583
  2. Ebb-and-Flow of Macroautophagy and Chaperone-Mediated Autophagy in Raji Cells Induced by Starvation and Arsenic Trioxide vol.15, pp.14, 2014, https://doi.org/10.7314/APJCP.2014.15.14.5715
  3. Recently Emerging Signaling Landscape of Ataxia-Telangiectasia Mutated (ATM) Kinase vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6485
  4. Silibinin Inhibits Proliferation, Induces Apoptosis and Causes Cell Cycle Arrest in Human Gastric Cancer MGC803 Cells Via STAT3 Pathway Inhibition vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6791
  5. Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells vol.16, pp.3, 2015, https://doi.org/10.7314/APJCP.2015.16.3.875
  6. Antitumor Activity of Chloroquine in Combination with Cisplatin in Human Gastric Cancer Xenografts vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3907
  7. Autophagic flux promotes cisplatin resistance in human ovarian carcinoma cells through ATP-mediated lysosomal function vol.47, pp.5, 2015, https://doi.org/10.3892/ijo.2015.3176
  8. CSC-3436 switched tamoxifen-induced autophagy to apoptosis through the inhibition of AMPK/mTOR pathway vol.23, pp.1, 2016, https://doi.org/10.1186/s12929-016-0275-y