非诺贝特联合顺铂对A549细胞上皮—间质转化及迁移侵袭能力的影响

摘要

Objective To investigate the effects of ppar alpha agonist fenofibrate combined with cisplatin on epithelial-interstitial transformation and the abilities of migration and invasion in lung cancer A549 cell line. Methods A549 cells were exposed to fenofibrate, cisplatin and fenofibrate combined with cisplatin respectively after 48 hours in vitro. MIT was employed to investigate proliferation and wound healing assay and the invasion chamber model were used to detect the effects of drug intervention on the migration and invasion of A549 cells. E-cadherin mRNAs and proteins in A549 cells were evaluated by RT-PCR and Western blot. Results Compared with the negative, fenofibrate combined with cisplatin could inhibit the proliferation of A549 and reduce the migration and metastatic abilities of A549 cells than either fenofibrate or cisplatin alone ( P < 0. 05). The expression of E-cadherin was up regulation and combined treatment group was better than separate treatment group (P<0.05). Conclusion Fenofibrate with cisplatin can inhibit the proliferation of A549 cells, decrease the migration and metastatic abilities of A549 cells, prevent epithelial-interstitial transformation of A549 cells, that may be a result of up -regulating E-cadherin.%目的 探索过氧化物酶体增殖因子激活受体α激动剂非诺贝特联合顺铂对人肺癌A459细胞上皮—间质转化及迁移侵袭能力的影响.方法 在体外分别采取单用非诺贝特,顺铂及两者联合干预A549细胞48h后,MTT比色法检测非诺贝特联合顺铂对A549细胞增殖的影响,细胞划痕实验和侵袭小室法检测对A549细胞迁移及侵袭运动能力的影响,RT-PCR和Westem blot实验检测上皮—间质转化相关因子E-cadherin的表达变化.结果 与阴性对照组相比,非诺贝特和顺铂单用与联合均能抑制A549细胞的增殖,减弱A549细胞的迁移侵袭运动能力,同时上调E-cadherin mRNA及蛋白水平的表达,其联合组的效果优于单用组(P＜0.05).结论 非诺贝特联用顺铂能够抑制A549细胞的生长,降低A549细胞的迁移侵袭运动能力,阻止A549细胞发生上皮—间质转化,其机制可能与增加E-cadherin的水平相关.