miR-21抑制替莫唑胺诱导U87细胞凋亡的体外实验研究  

miR- 21 confers apoptosis resistance to temozolomide in glioblastoma U87 cells in vitro

作　　者：杨鉴[1] 王颖毅[2] 何敖林[3] 王之敏[4] 石磊[1] 

机构地区：[1]江苏大学附属昆山医院神经外科,苏州215300 [2]南京医科大学第一附属医院神经外科 [3]江苏大学附属昆山医院中心实验室 [4]上海交通大学附属苏州九龙医院

出　　处：《中华神经外科杂志》2012年第3期304-308,共5页Chinese Journal of Neurosurgery

基　　金：基金项目：国家自然科学基金项目（81000963,81072078,30200335,30872657）;江苏省“333工程”培养资金资助项目（BRA2011046）;昆山社会发展项目基金（KS1006和KS1009）;苏州社会发展项目基金（SYS201063）

摘　　要：目的探讨miR-21过表达在替莫唑胺诱导胶质瘤U87细胞凋亡中的作用及其机制。方法miR-21过表达载体转染U87细胞，Hoeehst33258染色和流式细胞分析凋亡，Westernblot验证Bax和Bcl-2表达及检测Caspase-3活性。结果替莫唑胺可显著诱导U87细胞凋亡，上调Bax表达、下调Bcl-2表达及增加Caspase-3活性。U87细胞预转染miR-21过表达载体后，替莫唑胺的这种效应可部分被抑制。结论miR-21过表达可通过下调Bax／Bcl-2比率及Caspase-3活性部分抑制替莫唑胺诱导的U87细胞凋亡，提示胶质瘤中miR-21过表达可能是胶质瘤对替莫唑胺耐药的g 大新的因素。Objective To explore the function and mechanism of miR- 21 overexpression in glioblastoma U87 cells apoptosis induced by temozolomide （TMZ）. Methods miR- 21 over- expression vectors were transfected into U87 cells. After that, cell apoptosis was analyzed by Hoeehst 33258 staining and flow cytometry. And the expression of Bax and Bcl - 2 was identified by Western blot, while Caspase - 3 activity was detected. Results TMZ could effectively induce the apoptosis of U87 cells, upregulate the Bax expression, downregulate the Bcl -2 expression and increase PI3K activity. However,after U87 ceils were pre -transfected with miR -21 over- expression vectors, the effects induced by TMZ was partly inhibited. Conclusion Over - expression miR - 21 could inhibit TMZ - induced apoptosis in U87 cells, at least in part,by decreasing Bax/Bcl- 2 ratio and Caspase- 3 activity, which highlighted the possibility of miR -21 overexpression in resistance to chemotherapy TMZ in glioblastomas.

关 键 词：微RNAS 替莫唑胺 细胞凋亡 神经胶质瘤 

分 类 号：R739.4[医药卫生—肿瘤]