补中益气汤对TGF-β1诱导的肺腺癌荷瘤裸鼠移植瘤PI3K/AKT信号通路的影响

Effect of Buzhong Yiqi Decoction on PI3K/AKT signaling pathway in TGF-β1-induced lung adenocarcinoma xenograft of nude mice

目的:探讨补中益气汤干预上皮-间充质转化(EMT)改善肺腺癌顺铂耐药是否与PI3K/AKT信号通路相关。方法:取BALB/c裸鼠36只,随机分为6组:空载组(NG组)、模型组(MG组)、顺铂组(DDP组)、补中益气汤+顺铂组(BCD组)、顺铂+阻滞剂LY294002组(DLY组)、补中益气汤+顺铂+阻滞剂LY294002组(BCDLY组),TGF-β1过表达A549/DDP细胞接种于裸鼠左侧腋窝皮下,接种8 d后成瘤,开始给药。通过免疫组化、Western blot和RT-qPCR检测移植瘤PI3K、AKT、p-PI3K、p-AKT、E-cad、N-cad表达。结果:各组间PI3K、AKT表达差异性较小。与MG、DDP组相比,BCD、DLY、BCDLY组p-PI3K、p-AKT、N-cad表达显著下调,E-cad表达显著上调(P<0.05),BCDLY组表达变化最为显著。结论:补中益气汤能抑制肺腺癌荷瘤裸鼠移植瘤的EMT,改善顺铂耐药,可能与其抑制PI3K/AKT信号通路有关。

Objective:To investigate whether the intervention of Buzhong Yiqi Decoction on epithelial-mesenchymal transition(EMT)to improve cisplatin resistance in lung adenocarcinoma is related to PI3K/AKT signaling pathway.Methods:Thirty-six BALB/c nude mice were randomly divided into 6 groups:empty group(NG group),model group(MG group),cisplatin group(DDP group),Buzhong Yiqi Decoction+cisplatin group(BCD group),cisplatin+LY294002 group(DLY group),Buzhong Yiqi Decoction+cisplatin+LY294002 group(BCDLY group).A549/DDP cells with TGF-β1 overexpression were inoculated subcutaneously in left armpit of nude mice,and the xenograft was formed 8 days later,then the nude mice were administrated.Expressions of xenograft PI3K,AKT,p-PI3K,p-AKT,E-cad,N-cad were detected by immunohistochemistry,Western blot and RT-qPCR.Results:There was little difference in expressions of PI3K and AKT among groups.Compared with MG and DDP groups,expressions of p-PI3K,p-AKT and N-cad were down-regulated,however E-cad expression was up-regulated in BCD,DLY and BCDLY groups(P<0.05).There was the most significant change in BCDLY group.Conclusion:Buzhong Yiqi Decoction can inhibit EMT of xenograft of lung adenocarcinoma in nude mice and improve cisplatin resistance,which may relate to its inhibitory effect of PI3K/AKT signaling pathway.