肺复方通过PI3K/Akt/Nrf2信号通路对A549/DDP细胞耐药性的影响

Effect of Feifu Decoction on Drug Resistance in A549/DDP Cells Through PI3K/Akt/Nrf2 Signaling Pathway

目的观察肺复方对人肺癌顺铂耐药株A549/DDP细胞耐药性的作用及对PI3K/Akt/Nrf2信号通路的影响。方法选用A549/DDP细胞设立不含药血清的空白对照组、肺复方组、顺铂组、联合组,流式细胞术检测各组细胞周期分布和细胞中活性氧(ROS)的变化,Western blotting和RT-PCR检测PI3K/Akt/Nrf2信号通路及下游血红素氧合酶1(HO-1)、NAD(P)H:醌氧化还原酶1(NQO1)、多药耐药相关蛋白1(MRP1)的表达变化。结果与空白对照组、顺铂组相比,联合组引起细胞G1期阻滞,增加细胞内活性氧的累积,差异具有统计学意义(P<0.05或P<0.01);与空白对照组比,肺复方组和联合组能减少Nrf2核转位,下调p-Akt、HO-1、NQO1、MRP1蛋白表达和mRNA表达水平,差异具有统计学意义(P<0.05或P<0.01)。结论肺复方能够通过调控PI3K/Akt/Nrf2信号通路增加A549/DDP细胞对顺铂的敏感性。

Objective:To investigate the effect of Feifu Decoction combined with cisplatin on chemotherapy sensitization of lung cancer A549/DDP cells and its effect on PI3K/Akt/Nrf2 signal pathway.Methods:A549/DDP cells were selected to establish drug-free serum control group,Feifu Decoction group,cisplatin group and combined group.The cell cycle distribution and the changes of reactive oxygen species(ROS)in cells were detected by flow cytometry.Western blotting and RT-PCR were used to detect the expression of PI3K/Akt/Nrf2 signal pathway and downstream heme oxygenase-1(HO-1),NAD(P)h:quinone oxidoreductase 1(NQO1),multidrug resistance associated protein 1(MRP1).Results:Compared with the control group and cisplatin group,the combined group caused Gl phase arrest and increased the accumulation of intracellular ROS,which was statistically significant(P<0.05 or P<0.01).Compared with the control group,Feifu Decoction group and combined group could reduce Nrf2 nuclear translocation and down-regulate the protein expression and mRNA expression levels of p-Akt,HO-1,NQO1 and MRP1,which was statistically significant(P<0.05 or P<0.01).Conclusion:Feifu Decoction can increase the sensitivity of A549/DDP cells to cisplatin by regulating PI3K/Akt/Nrf2 signaling pathway.