柴胡蚤休汤治疗肝细胞癌关键靶点的网络药理学研究及预后模型的建立  

Network pharmacological study on key targets of Chaihu Zaoxiu decoction in the treatment of hepatocellular cancer and establishment of prognostic models

作　　者：唐屿 池晴佳 田菲菲[1] 封顺[1] TANG Yu;CHI Qingjia;TIAN Feifei;FENG Shun(School of Life Sciences and Engineering,Southwest Jiaotong University,Chengdu,Sichuan,610031 P.R.China;College of Science,Wuhan University of Technology,Wuhan,Hubei,430070 P.R.China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610031 [2]武汉理工大学理学院,湖北武汉430070

出　　处：《华西药学杂志》2024年第1期18-24,共7页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:22174117)。

摘　　要：目的采用网络药理学研究柴胡蚤休汤治疗肝细胞癌的关键靶点,并构建风险评分模型用于解决肝癌的预后问题。方法通过网络药理学、LASSO COX建模和体外细胞实验方法,探讨柴胡蚤休汤治疗肝细胞癌的主要药用活性成分、作用分子靶点及相关基因预后能力。结果柴胡蚤休汤可能通过作用于ESR1、G6PD、AKR1C3、NQO1、CDK1等关键靶点和p53信号通路发挥治疗肝细胞癌的作用。这些关键靶点与活性成分分子对接的结合性良好。构建治疗靶点风险评分模型表明:其具有良好的预后效果和独立预后能力。柴胡蚤休汤对体外人肝癌细胞HepG2的细胞毒性具有浓度和时间依赖,且能够显著抑制G6PD、CDK1核心靶点的表达。结论柴胡蚤休汤可通过调控G6PD、CDK1关键靶点和p53信号通路治疗肝细胞癌,基于G6PD、CDK1关键靶点建立的新型风险评分模型对肝细胞癌具有良好的独立预后功能。可为后续研究提供新思路。OBJECTIVE To investigate the key targets of Chaihu Zaoxiu decoction(CZD)in the treatment of hepatocellular carcinoma using network pharmacology,and to construct a risk score model to address the prognosis of hepatocellular carcinoma by quantitative means.METHODS The main medicinal active ingredients,the molecular targets of action and the prognostic ability of related genes in CZD for the treatment of hepatocellular carcinoma were investigated by network pharmacology,LASSO COX modelling and in vitro cellular assay methods.RESULTS CZD may act through key targets of ESR1,G6PD,AKR1C3,NQO1 and CDK1,and the p53 signaling pathways to treat hepatocellular carcinoma.Molecular docking results showed good binding of these key targets to the active ingredients.The risk score model based on LASSO COX indicated that it owned good prognostic effect and independent prognostic ability.In vitro experiments demonstrated that CZD was concentration-dependent and time-dependent in its cytotoxicity against human hepatoma HepG2 cells and was able to significantly inhibit the expression of two core targets,G6PD and CDK1.CONCLUSION CZD can treat hepatocellular carcinoma by modulating key targets of G6PD and CDK1,and signaling pathway of p53,and the novel risk scoring model built with G6PD and CDK1 indicates good independent prognostic function for hepatocellular carcinoma.This study provides new ideas for subsequent network pharmacology research.

关 键 词：柴胡蚤休汤 活性成分 网络药理学 肝细胞癌 分子对接 风险评分模型 肝癌预后 体外细胞实验 

分 类 号：R96[医药卫生—药理学]