摘要
目的:观察塞来昔布对人胃癌细胞株SGC-7901凋亡和自噬的影响,并探讨其凋亡的机制。方法:不同浓度塞来昔布处理SGC-7901细胞后,MTT法检测SGC-7901细胞的增殖,TUNEL法检测SGC-7901细胞的凋亡,透射电镜观察SGC-7901细胞超微结构的改变,流式细胞术检测SGC-7901细胞的凋亡率,实时定量荧光PCR法检测SGC-7901细胞中caspase-8和caspase-9 mRNA的表达。结果:塞来昔布时间(24、48、72 h)和剂量(50、75、100、125μmol/L)依赖性抑制SGC-7901细胞的增殖,125μmol/L塞来昔布作用SGC-7901 72 h细胞的增殖抑制率高达(85.6±4.51)%。塞来昔布可诱导SGC-7901细胞凋亡,透射电镜下观察到典型的凋亡小体和自噬体,细胞凋亡率从(2.2±1.32)%上升到(35.7±5.73)%(P<0.01)。塞来昔布作用后,SGC-7901细胞中caspase-8和caspase-9 mRNA表达明显增加,呈时间和剂量依赖性(P<0.05)。结论:塞来昔布通过激活依赖caspase-8的死亡受体途径和依赖caspase-9的线粒体途径诱导胃癌SGC-7901细胞凋亡,同时诱发自噬性细胞死亡。
Objective：To observe the effect of celecoxib on apoptosis and autophagy of human gastric cancer cell line SGC-7901,and to investigate the mechanism of apoptosis.Methods： SGC-7901 cells were treated with different concentrations of celecoxib,proliferation of SGC-7901 cells was studied by MTT assay,apoptosis was assessed by TUNEL,ultrastructure changes was observed by transmission electron microscopy,apoptotic rate was examined by flow cytometry,and expression of caspase-8,caspase-9 mRNA was analyzed by real-time quantitative PCR.Results： Celecoxib inhibited proliferation of SGC-7901 cells in a time-and dose-dependent manner,with inhibitory rate of（85.6±4.51）% at 125 μmol/L celecoxib for 72 h.Celecoxib induced apoptosis of SGC-7901 cells,typical apoptotic body and autophagosome were observed under TEM,and apoptotic rate increased from（2.2±1.32）% to（35.7±5.73）%（P0.05） as detected by FCM.Expression of caspase-8 and caspase-9 mRNA increased sharply in SGC-7901 cells treated with celecoxib in a time-and dose-dependent manner.Conclusion： Celecoxib can induce apoptosis of gastric cancer SGC-7901 cells by activating caspase-8 in the death-receptor pathway and caspase-9 in the mitochondrial pathway,and induce autophagic cell death.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2011年第5期514-518,共5页
Chinese Journal of Cancer Biotherapy
基金
国家自然科学基金资助项目(No.30872478)
甘肃省技术研究与开发专项计划资助项目(No.0912TCYA027)~~
关键词
塞来昔布
胃癌细胞
凋亡
自噬
celecoxib
gastric cancer
apoptosis
autophagy
