过表达miR-21通过PI3K-AKT 通路抑制替莫唑胺对胶质瘤U87细胞的增殖抑制作用

目的 探讨miR-21 过表达在替莫唑胺(TMZ)诱导胶质瘤U87 细胞增殖中的作用及其机制,明确miR-21 过表达在替莫唑胺临床治疗胶质瘤耐药中的作用.方法 Pre-miR-21 过表达载体转染U87 细胞,通过形态学观察,噻唑蓝(MTT)试验检测细胞增殖情况.Western 印迹验证Akt 和p-Akt 表达及检测PI3K 活性.结果 替莫唑胺可显著抑制U87 细胞生长,下调Akt 和p-Akt 表达及抑制PI3K 活性.U87 细胞预转染pre-miR-21 过表达载体后,替莫唑胺的这种效应可部分被miR-21 过表达所抑制.结论 miR-21 过表达可通过活化PI3K-AKT 通路部分抑制替莫唑胺诱导的U87 细胞凋亡,提示胶质瘤中miR-21 过表达可能是替莫唑胺临床治疗胶质瘤药物抵抗的一大新的因素.

Overexpression of miR-21 in glioblastoma U87 cells confers proliferation resistance to Temozolomide via PI3K-AKT pathway

Objective To explore the function and mechanism of miR-21 overexpression in glioblastoma U87 cells proliferation inhibition induced by Temozolomide （TMZ）. Methods Pre- miR-21 over-expression vectors were transfected into U87 cells. And the effects of cell proliferation were evaluated by morphological observation and MTT assay. The expressions of Akt and p-Akt were identified by Western blot, while PI3 K activity was detected. Results TMZ could effectively inhibit the growth of U87 cells, downregulate Akt and p-Akt expressions and inhibit PI3K activity. After U87 cells were pre-transfected pre-miR-21 over-expression vectors, the effects induced by TMZ with partly inhibited by miR-21 overexpression. Conclusions Over-express miR-21 may inhibit TMZ- induced apoptosis in U87 cells via PI3K-AKT pathway, which highlight the possibility of miR-21 overexpression in the clinical resistance to chemotherapeutic therapy of TMZ.