格尔德霉素增强子宫颈癌HeLa细胞热疗效的影响  

Study on geldanamycin of promoting heat-induced cell killing of cervix cancer HeLa cells

作　　者：苟永胜[1] 裘秀春[1] 马保安[1] 周勇[1] 张明华[1] 钱济先[1] 青晓芬[1] 任民[1] 范清宇[1] 

机构地区：[1]第四军医大学唐都医院全军骨肿瘤研究所,陕西西安710038

出　　处：《中国癌症杂志》2007年第6期444-447,共4页China Oncology

基　　金：中国博士后基金资助(No2005038259)

摘　　要：背景与目的:苯醌安莎霉素类如格尔德霉素(geldanamycin,GA)通过抑制热休克蛋白(heat shock protain90,HSP90)从而导致细胞内信号调节通路网络的多点阻断,如导致涉及细胞增殖、细胞周期调节及幸存调节等众多效应蛋白的降解。前期研究证明HSP90可作为抗肿瘤治疗的一个分子靶位。本研究以子宫颈癌HeLa细胞为研究对象,观察HSP90分子伴侣复合物阻止剂格尔德霉素能否增强加热对HeLa细胞的杀伤效应。方法:采用四唑盐比色实验(MTT)、流式细胞术(flow cytometry,FCM)、吖啶橙荧光染色等方法观察比较应用单纯热疗组、GA组、热疗联合GA组对HeLa细胞活力、凋亡率及细胞形态学的影响。结果:四唑盐比色实验观察到加热与GA化疗间有交互作用,加热联合GA组显著增强单独加热对HeLa细胞杀伤效应(P<0.01);Annexin V-FITC染色流式细胞术结果显示加热联合GA组、单纯加热组、单纯GA治疗组所致细胞凋亡率分别为92.1%、52.2%及26.8%。用吖啶橙荧光染色法观察到加热联合GA组明显见HeLa细胞固缩着色不均而且较深,细胞核浓缩、裂解等凋亡特征。结论:HSP90分子伴侣复合物阻止剂GA能增强热诱导的HeLa细胞的杀伤作用。Background and purpose： Ansamycin antibiotics , such as geldanamycin（GA）, inhibit function of HSP90, causing selective degradation of several intracellular proteins regulating such processes as proliferation, cell cycle regulation, and prosurvival signaling cascades. Heat shock protein 90（HSP90） has been identified previously as a molecular target for anticancer agents. Therefore, the purpose of this essay was to examine the capability of a HSP90 chaperone complex inhibitor, geldanamycin, of heat-induced cell killing of HeLa cells. Methods： The HeLa cells was incubated with GA during heat treatment. The surviving rates were determined by MTT assay test ; the rates of apoptosis were analyzed by flow cytometry （ FCM）. At the same time, morphologic changes of HeLa cells were observed by acridine orange staining in these groups of different treatment. Results： MqT assays suggested the interaction between heat and GA treatment, showed that GA in combination with heat synergistically potentiated heat-induced cell killing（ P 〈0.01） . Annexin V-FITC staining revealed that the percentages of apoptotic cells in the group of combination of heat with GA were 92. 1%, 52.2% in the group of heat alone and 26.8% in the group of GA alone. Similiarly, cell shrinkage and nuclear condensation in the group of combination of heat with GA were observed by acridine orange staining. Conclusions： The HSP90 chaperone complex inhibitor（GA） potentiated heat-induced cell killing of HeLa cells.

关 键 词：热休克蛋白90(HSP90) 热疗 细胞凋亡 子宫颈癌细胞 

分 类 号：R73-36[医药卫生—肿瘤]