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

作　　者：谭小宁[1] 梁子成 柳卓 邱云[1] Tan Xiaoning;Liang Zicheng;Liu Zhuo;Qiu Yun(The Affiliated Hospital of Hunan Academy of Chinese Medicine,Hunan Key Laboratory of Chinese Medicine Oncology,Hunan,Changsha 410006,China)

机构地区：[1]湖南省中医药研究院附属医院,中医肿瘤学湖南省重点实验室,湖南省中西医结合肿瘤临床研究中心,湖南长沙410006

出　　处：《中国中医急症》2024年第6期963-967,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：湖南省重点研发项目(2023SK2057);湖南省自然科学基金(2022JJ40238);湖南省中医药计划项目(2021173,D2022064);湖南省卫健委课题(202113051181,202203105606);长沙市自然基金(kq2202478);全国中药特色技术传承人才培训项目(国中医药人教函[2023]96号);湖南省十四五中医药骨干人才(湘中医药[2024]3号)。

摘　　要：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.

关 键 词：肺癌 肺复方 A549/DDP细胞 PI3K/Akt/Nrf2信号通路 耐药性 

分 类 号：R285.5[医药卫生—中药学]