氯喹促进顺铂诱导胃癌SGC7901细胞凋亡及其机制  

Chloroquine promotes DDP-induced apoptosis in human gastric cancer cell line SGC7901

作　　者：张慧卿[1] 方念[2] 芦珊[1] 何波[1] 万以叶[1] 

机构地区：[1]江西省肿瘤医院内三科,南昌市330029 [2]南昌大学第四附属医院消化内科

出　　处：《中国肿瘤临床》2013年第16期947-950,共4页Chinese Journal of Clinical Oncology

基　　金：江西省青年自然基金项目(编号:20122BAB215029)资助~~

摘　　要：目的:研究自噬对顺铂(cisplatin,DDP)诱导的胃癌SGC7901细胞凋亡的影响,并初步探讨其可能机制。方法:DDP和(或)氯喹处理胃癌SGC7901细胞,MTT法检测细胞增殖,流式细胞术检测细胞凋亡,MDC染色后荧光显微镜观察自噬囊泡,West ern Blot检测自噬和凋亡相关蛋白。结果:5 mg/L的顺铂作用于胃癌SGC7901细胞24 h,细胞凋亡率为21.07%±2.12%,同时观测到自噬囊泡增多和LC3-Ⅱ蛋白表达升高;氯喹特异性抑制自噬活性后,提高了顺铂诱导的细胞凋亡率(30.16%±3.54%,P<0.05);检测到凋亡相关蛋白Caspase-3和P53表达增加,Bcl-2蛋白表达下降。结论:自噬在顺铂诱导胃癌SGC7901细胞凋亡的过程中起保护作用,氯喹抑制自噬后,可能通过激活P53蛋白及灭活Bcl-2蛋白的表达来促进细胞凋亡,联合应用顺铂和氯喹有望成为胃癌治疗的新策略。Objective： To investigate the mechanism and effects of autophagy on cisplatin（DDP）-induced apoptosis in human gas- tric cancer cell line SGC7901. Methods： Cell proliferation was determined by an MTT assay after the SGC7901 cells were treated with DDP and/or chloroquine. Cell apoptosis was determined by flow cytometry. Autophagy and related protein expressions were detected by Western blot. Autophagy was quantitatively analyzed by fluorescence microscopy after monodansylcadaverine staining was per- formed. Results： The cells were treated with 5 mg/L of DDP for 24 h, the rate of cell apoptosis was （21.07±2.12）%. Autophagy, char- acterized by an increase in the number of autophagic vesicles and LC3-II protein level, was observed in DDP-treated cells. After autoph- agy was inhibited by chloroquine, the rate of cell apoptosis was increased to （30.16± 3.54）%. In addition, caspase-3 and P53 protein levels were increased, but Bcl-2 protein was decreased. Conclusion： Autophagy protected human gastric cancer cell line SGC7901 from DDP-induced apoptosis. In addition, the inhibition of autophagy could promote apoptosis. The combined therapy of DDP and chlo- roquine may be a promising therapeutic strategy for gastric cancer.

关 键 词：自噬 顺铂 氯喹 凋亡 胃癌 

分 类 号：R735.2[医药卫生—肿瘤]