苯扎贝特协同顺铂抑制肺腺癌细胞生长和诱导凋亡  

Inhibition effects of bezafibrate in coordination with cisplatin on cell growth and inducing apoptosis of lung adenocarcinoma cells

作　　者：王桂平[1] 张彦焘[1] 刘新艳[2] 潘学兵[1] 周琼[1] 郭俐麟[1] 

机构地区：[1]广州医科大学卫生职业技术学院药学系,广东广州510180 [2]广州医科大学药物研究中心,广东广州510182

出　　处：《药学研究》2014年第11期621-625,共5页Journal of Pharmaceutical Research

基　　金：广东省自然科学基金项目(No.S2011010004147);广州医科大学2011年科研基金博士启动基金(No.2011C06)

摘　　要：目的观察过氧化物酶体增殖因子激活受体α(PPARα)激动剂苯扎贝特联用顺铂对肺腺癌A549细胞增殖抑制和诱导凋亡的协同效应及可能机制。方法采用CCK8法测定不同浓度苯扎贝特处理A549细胞的生长曲线,观察苯扎贝特、顺铂及两药联用对A549细胞的生长抑制作用,并应用中效原理评价两药联用效应;采用流式细胞技术分析苯扎贝特与顺铂联用对细胞凋亡的诱导作用,并通过qRT-PCR检测A549细胞中VEGF和HIF-1αmRNA的表达变化。结果苯扎贝特联合顺铂呈现明显协同抑制效应,两药联用时IC50值为15.92μmol·L-1,当苯扎贝特浓度小于588μmol·L-1,顺铂浓度小于206μmol·L-1,CI值小于1,即两药合用均产生协同作用。联合用药组细胞凋亡率明显高于单药组(P<0.05),并且联合用药组较单药组显著下调VEGF和HIF-1αmRNA的表达,差异有统计学意义(P<0.05)。结论苯扎贝特联合顺铂对肺癌细胞具有协同抑制效应,并可有效诱导细胞凋亡,其机制可能与下调VEGF和HIF-1α的表达有关。Objective To observe the effects of peroxisome proliferator-activated receptorα（ PPARα）agonist bezaf-ibrate combinated with cisplatin（ DDP）on proliferation and apoptosis of lung adenocarcinoma（ AC）A549 cell and the pos-sible mechanism. MetHods CCK8 kit assay was used to detect growth inhibiton curve of A549 cells treated with various concentrations of bezafibrate. The median-effect method was used to evaluate the combination effect. Cell apoptosis was e-valuated with flow cytometry,and the expression of VEGF and HIF-1αmRNA were analyzed using real-time PCR（ qRT-PCR）. Results Bezafibrate combinated with DDP showed significately synergy inhibition effect,and the IC50 was 15. 92μmol·L-1 when the two agents were combined. The combination index（CI）was less than 1 when the concentration of bez-afibrate〈588 μmol·L-1 and cisplatin〈206 μmol·L-1 ,namely two drugs combination showed synergy effect. The cell apoptosis rate of A549 cells was significately higher than single drug group（P〈0. 05）. The expression level of VEGF and HIF-1α mRNA were significately lower in combination group than in bezafibrate or cisplatin group（P〈0. 05）. CoNclu-sioN Our results demonstrated that bezafibrate combinated with cisplatin showed synergy inhibition effect on lung AC, which may be related with the down-expression of VEGF and HIF-1α.

关 键 词：苯扎贝特 顺铂 肺腺癌 协同效应 过氧化物酶体增殖物激活受体 

分 类 号：R979.1[医药卫生—药品]