非诺贝特联用顺铂对人肺癌A549细胞抑制和凋亡的实验研究

目的探讨过氧化物酶体增殖因子激活受体仪激动剂非诺贝特联用顺铂对体外培养的人肺癌A549细胞增殖和凋广的影响及可能机制。方法采用MTF法分别检测单用非诺贝特、顺铂和非诺贝特联用顺铂对肺癌A549细胞的生长抑制情况。采用Hoechest染色观察非诺贝特联用顺铂对肺癌A549细胞的生长抑制作用。流式细胞术检测联合用药对A549细胞的凋亡诱导作用。RT—PCR法检测联合用药对A549细胞中caspase－3、survivinmRNA的表达变化情况。结果非诺贝特对肺癌A549细胞有抑制作用，呈现时间剂量关系。联合用药组作用肺癌A549细胞48h后比单用药组的细胞抑制作用强（P〈0．05）。形态学观察及流式细胞术结果显示联合用药组A549凋亡细胞数目多于单药组，RT—PCR结果提示联合用药组较单用药组上调caspase－3mRNA的表达，下调stirvivin mRNA的表达。结论非诺贝特与顺铂联用可以增强顺铂杀伤肺癌A549细胞作用，其机制可能与上调caspase－3的表达和下调survivin的表达有关。

Experimental study of fenofibrate combined with cisplatin on inhibition and apoptosis of human lung cancer A549 cell line

Objective To investigate the effects of peroxisome proliferator-activated receptor α agonist fenofibrate combined with cisplatin on proliferation and apoptosis of human lung cancer A549 cell line and the possible mechanism. Methods A549 cells were exposed to fenofibrate, cisplatin and fenofibrate combined with cisplatin respectively. MTT method was used to investigate proliferation. Hoechest stain was applied to analyze the apoptosis effects. Flow cytometry was used to detect the apoptosis. A549 cells caspase-3 and survivin mRNA expression changes after treatments were detected by RT-PCR. Results Fenofibrate could inhibit the proliferation of A549 cells in dose-time relationship. Compared with either fenofibrate or cisplatin alone, combining fenofibrate with cisplatin increased the growth inhibition rate of A549 cells （P 〈 0.05 ）. More apoptotic cells were detected in combined treatment group than separate treatment group by Hoechest stain and flow cytometry. RT-PCR results showed the expression of caspase-3 mRNA was up regulation, then the expression of survivin mRNA was down regulation. Conclusion Combining fenofibrate with cisplatin can enhance the role of cisplatin killing lung cancer A549 cells, which may be a result of up-regulating caspase-3 and down-regulating survivin.