益气解毒方抑瘤作用及生物信息分析

摘要

Objective To observe the inhibitory effects of Yiqi Jiedu Recipe(YJR)on transplanted Lewis lung cancer in mice and to explore its relative mechanism. Methods In-vivo mouse model of transplanted Lewis lung cancer was established. Twenty modeled mice were divided into model group,low- and high-dose YJR groups, and cisplatin group, 5 mice in each group. After treatment, the mouse general situations, body mass, body mass excluding tumor mass,tumor mass,tumor index,tumor volume,and tumor-inhibition rate were detected. In the in-vitro experiments, the inhibitory effect of YJR on the proliferation of A549 and H1299 cells was evaluated by CCK8 assays, and the effect of YJR on the apoptosis of A549 and H1299 cells was evaluated by flow cytometry assay. Bioinformatics analysis was carried out to identify the critical function,pathways and genes with bioinformatics mining method. Results Compared with the model group, high-dose YJR group and cisplatin group significantly inhibited the tumor growth of the transplanted Lewis lung cancer in mice(P<0.05 or P < 0.001). The experimental results in vitro showed that YJR significantly inhibited lung cell growth, and induced lung cell apoptosis. Bioinformatics analysis results showed that the inhibitory effects of YJR was probably related to multiple paths including apoptosis,cell cycle,autophagy,etc.,and promoting apoptosis may be the important way. YJR played a role in promoting apoptosis via AKT, HSP90, BCL2, CASP9 and activation of PI3K-AKT pathway. Conclusion YJR exhibits anti-tumor actions through regulating the targets AKT,HSP90, BCL2, CASP9 and affecting PI3K-AKT pathway to promote apoptosis and inhibit cell proliferation, thus to suppress the growth of transplanted tumor.%[目的]探讨益气解毒方对肺癌Lewis细胞小鼠移植瘤的抑制作用及其可能的机制.[方法]体内实验:复制Lewis细胞小鼠移植瘤模型;将20只造模小鼠分为模型组,中药低、高剂量组,顺铂组,每组5只;给药结束后,观察各组小鼠一般状况、体质量、去瘤体质量、瘤体质量、肿瘤指数、肿瘤体积及抑瘤率的变化.体外实验:采用CCK8法观察益气解毒方对A549和H1299细胞株增殖的抑制情况,采用流式细胞术观察益气解毒方对A549和H1299细胞株的促凋亡作用.生物信息分析:采用生物信息挖掘的方法探索其可能的作用途径、信号通路和作用靶点.[结果]与模型组比较,中药高剂量组、顺铂组对移植瘤的生长均具有明显的抑制作用(P<0.05或P<0.001).体外实验结果显示,益气解毒方可明显抑制肺癌细胞增殖,并促进肺癌细胞凋亡.生物信息分析结果提示益气解毒方抑制肺癌作用可能涉及凋亡、细胞周期、自噬等多种途径,其中促进凋亡可能是其主要途径,促凋亡作用可能通过影响AKT、HSP90、BCL2、CASP9等靶点的表达,调节PI3K-AKT等信号通路来实现.[结论]益气解毒方可能通过调节AKT、HSP90、BCL2、CASP9等靶点,影响PI3K-AKT等信号通路来促进凋亡,抑制细胞增殖,进而抑制肺癌移植瘤的生长,发挥抑瘤作用.