Protective autophagy antagonizes oxaliplatin-induced apoptosis in gastric cancer cells.
- Author:
Ling XU
1
;
Xiu-Juan QU
;
Yun-Peng LIU
;
Ying-Ying XU
;
Jing LIU
;
Ke-Zuo HOU
;
Ye ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Apoptosis; drug effects; Autophagy; drug effects; Caspase 3; metabolism; Caspase 8; metabolism; Cell Line, Tumor; Cell Proliferation; drug effects; Humans; Organoplatinum Compounds; pharmacology; Phosphatidylinositol 3-Kinase; metabolism; Poly(ADP-ribose) Polymerases; metabolism; Proto-Oncogene Proteins c-akt; metabolism; Signal Transduction; drug effects; Stomach Neoplasms; metabolism; pathology; TOR Serine-Threonine Kinases; metabolism
- From:Chinese Journal of Cancer 2011;30(7):490-496
- CountryChina
- Language:English
- Abstract: Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 μg/mL oxaliplatin for 24 h, respectively. In addition, caspase activation and poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-II protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer.
