首页|基于网络药理学和实验验证探讨益气柔肝解毒方治疗肝癌的作用机制

基于网络药理学和实验验证探讨益气柔肝解毒方治疗肝癌的作用机制

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目的:基于网络药理学和实验验证探讨益气柔肝解毒方治疗肝细胞癌(HCC)的分子作用机制.方法:通过网络药理学方法获得益气柔肝解毒方调控HCC的潜在靶点及信号通路.通过动物实验构建荷瘤(肝癌细胞H22 皮下移植瘤)小鼠模型,给予不同剂量组的益气柔肝解毒方治疗后,评价肿瘤组织的生长情况、HE染色检测小鼠肿瘤组织病理改变、WB检测肿瘤组织PI3K/AKT/NFκB信号通路蛋白的表达情况.结果:网络药理学分析共得到活性化合物64 个,与疾病靶点交集的潜在靶点236 个,核心靶点24 个,益气柔肝解毒方可能通过影响TP53、ALB、PTEN、CCND1 等肝癌常见的突变基因,调控Th1、Th2、Th17 等细胞分化,下调PD-1 检查点与PD-L1 表达,以及阻断PI3K/AKT、NFκB等肝癌异常激活的关键信号通路来发挥抗肿瘤效应.实验结果表明:与模型组相比,益气柔肝解毒方能抑制荷瘤小鼠肿瘤体积增长,显著降低PI3K/AKT/NFκB通路蛋白的表达.结论:益气柔肝解毒方能通过多成分、多靶点及多途径发挥治疗HCC的作用,并可能通过影响PI3K/AKT/NFκB信号通路,抑制肝癌的发展.
Investigation into the mechanism of action of the Yiqi Rougan Jiedu formula in the treatment of liver cancer based on network pharmacology and experi-mental validation
Objective:To explore the molecular mechanisms of Yiqi Rougan Jiedu formula in treating hepatocellular carcinoma(HCC)based on network pharmacology and experimental validation.Methods:Potential targets and signaling pathways regulated by the herbal formula for HCC were obtained through network pharmacology.A mouse model with H22 hepatocellular carcinoma cell subcutaneous transplantation tumor was established for animal experiments.Different doses of yiqi Rougan Jiedu formula were administered,and the growth of tumor tissues,HE staining of mouse tumor tissues,and WB detection of PI3K/AKT/NFκB signaling pathway protein expression in tumor tissues were evaluated.Results:Network pharmacology showed that 64 active compounds were identified,with 236 potential targets intersecting disease targets,including 24 core targets.yiqi Rougan Jiedu formula may affect common mutated genes in liver cancer such as TP53,ALB,PTEN,CCND1;regulate Th1,Th2,Th17 cell differentiation,downregulate PD-1 checkpoint and PD-L1 expression,as well as block key signaling pathways such as PI3K/AKT and NFκB to exert anti-tumor effects.Experimental results indicated that compared to the model group,yiqi Rougan Jiedu formula could inhibit tumor volume growth in mice carrying tumors and significantly reduce expression of proteins in the PI3K/AKT/NFκB pathway.Conclusion:yiqi Rougan Jiedu formula may play a role in treating HCC through multiple components,multiple targets,and multiple pathways by potentially affecting the PI3K/AKT/NFκB signaling pathway to inhibit liver cancer development.

yiqi Rougan Jiedu formulaliver cancernetwork pharmacologyPI3K-AKT signaling pathway

周朝炜、徐春军、武璇

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北京中医药大学临床医学院(北京,100029)

首都医科大学附属北京中医医院肝病科

益气柔肝解毒方 肝癌 网络药理学 PI3K-AKT信号通路

北京中医医院院级课题暨两院合作课题北京中医医院"宽街明医"工作室——徐春军工作室

LYZD202205276-2023

2024

中西医结合肝病杂志
中国中西医结合学会,湖北中医学院

中西医结合肝病杂志

CSTPCD
影响因子:0.908
ISSN:1005-0264
年,卷(期):2024.34(10)