HSP90抑制剂17-AAG对胃癌SGC-7901细胞生长周期和凋亡的影响  

Effects of HSP90 inhibitor 17-AAG on cell cycle and apoptosis of human gastric cancer cell lines SGC-7901

作　　者：陈美霓[1] 许静洪[1] 赵菊梅[1] 

机构地区：[1]延安大学医学院实验中心,陕西延安716000

出　　处：《南方医科大学学报》2013年第2期271-275,共5页Journal of Southern Medical University

基　　金：陕西省教育厅科学研究项目(12JK0713);2012年延安大学自然科学专项基金项目(ydz2012-03)

摘　　要：目的研究一种特异性的热休克蛋白90抑制剂17-丙烯胺基-17-去甲氧基格尔德霉素(17-AAG)对人胃癌细胞SGC-7901细胞增殖和凋亡的影响,分析其可能的作用机制。方法应用MTT比色法检测不同浓度的17-AAG对胃癌SGC-7901细胞的生长抑制率;荧光显微镜下观察PI染色的SGC-7901细胞凋亡形态学变化;采用流式细胞术检测SGC-7901细胞的细胞周期变化及凋亡率变化;通过免疫组化检测胃癌SGC-7901细胞中Fas蛋白的表达。结果 MTT法显示17-AAG能明显抑制胃癌SGC-7901细胞的生长增殖,呈时间、剂量依赖性;流式细胞仪细胞周期分析显示,17-AAG处理48 h后使SGC-7901细胞发生G2/M期阻滞,并有诱导SGC-7901细胞凋亡的作用;细胞免疫组化结果显示,SGC-7901细胞胞浆内有Fas表达,随着药物浓度的加大,阳性表达率也逐渐增加。结论 17-AAG通过改变细胞周期、诱导其凋亡来抑制胃癌SGC-7901细胞的增殖,上调SGC-7901细胞中Fas蛋白的表达是诱导凋亡的作用机制之一。Objective To study the effect of the HSP90 inhibitor, 17-allylamino-17-demethoxygelda-namycin （17-AAG）, on cell proliferation and apoptosis of human cancer SGC-7901 cells and explore the mechanisms. Methods The inhibitory effect of 17-AAG on the proliferation and morphology of SGC-7901 cells was assessed with MTT assay and DNA-PI staining, respectively. Flow cytometry was employed to analyze the changes in cell cycle and apoptosis of the cells following 17-AAG exposure. The cellular expression of Fas protein was detected by immunohistochemistry. Results 17-AAG significantly suppressed the proliferation of SGC-7901 cells in a time- and dose-dependent manner. After treatment with 17-AAG for 48 h, SGC-7901 cells showed cell cyde arrested at GdM stage, and the cell apoptosis rate increased with the 17-AAG concentration. The expression of Fas protein in the cytoplasm of SGC-7901 cells increased gradually with the increase of 17-AAG concentration. Conclusion 17-AAG can induce apoptosis, alters the cell cycle distribution and up-regulates the expression of Fas protein in SGC-7901 cells to suppress the cell proliferation.

关 键 词：17-AAG 胃癌 SGC-7901 细胞凋亡 FAS蛋白 

分 类 号：R735.2[医药卫生—肿瘤]