氟奋乃静通过自噬诱导U87胶质瘤细胞死亡及其机制探讨  

Fluphenazine induced autophagic cell death and its mechanisms in human U87 glioma cell

作　　者：沈蔷[1] 曹桂丽[1] 于国泳[2] 

机构地区：[1]东城区社区卫生服务管理中心质量管理部,北京100010 [2]北京中医药大学东直门医院肾病内分泌科,北京1007000

出　　处：《癌症进展》2016年第8期744-747,共4页Oncology Progress

摘　　要：目的观察氟奋乃静(FPZ)通过自噬诱导U87胶质瘤细胞死亡的机制。方法体外培养U87胶质瘤细胞并经FPZ处理,采用细胞活力和集落形成方法分析细胞的生存率,采用Western blot检测自噬相关蛋白及PI3K/AKT/m TOR通路蛋白的表达。结果 FPZ处理后,U87胶质瘤细胞活力显著降低(P﹤0.05),菌落数显著降低(P﹤0.05);微管相关蛋白1轻链3-Ⅱ型(LC3-Ⅱ)显著增加,并呈时间和剂量依赖性;p-AKT水平及其下游pm TOR水平显著下降,并呈时间依赖性。采用PI3K抑制剂LY294002处理U87胶质瘤细胞后,LC3-Ⅱ生成明显增加。结论 FPZ可通过抑制PI3K/AKT/m TOR通路调节自噬,发挥细胞毒性作用。Objective To investigate the role of autophagy in fluphenazine （FPZ）-induced cytotoxicity in U87 glio-ma cells. Method U87 glioma cell was cultured in vitro and then treated with FPZ; The survival rate of U87 glioma cells was assessed by cell viability and clonogenic survival assay;The autophagy related protein and PI3K/AKT/mTOR pathway protein were determined by using western blot. Result FPZ treatment inhibited cell viability and long-term clo-nogenic survival of U87 glioma cells （both P〈0.05）. Additionally, FPZ triggered autophagy, as indicated by the time-and dose-dependent accumulation of microtubule-associated protein 1 light chain 3 （LC3-II）, while the level of p-AKT and the downstream p-mTOR was decreased as time elapsed. Treatment with LY294002, a PI3K inhibitor, increased the accu-mulation of LC3-II. Conclusion These results provided the evidence that FPZ-induced cytotoxicity is mediated through autophagic cell death in U87 glioma cells by inhibiting PI3K/AKT/mTOR pathway.

关 键 词：氟奋乃静 自噬 胶质瘤细胞 死亡 

分 类 号：R739.4[医药卫生—肿瘤]