基于网络药理学和分子对接探讨槲芪散治疗原发性肝癌作用机制  

Exploration of Mechanism of Action of Huqi San in Treatment of Primary Liver Cancer Based on Network Pharmacology and Molecular Docking

作　　者：沈飞[1] 张盛[1] 陈英杰[1] SHEN Fei;ZHANG Sheng;CHEN Yingjie(Department of General Surgery,The Third People's Hospital of Changzhou,Changzhou Jiangsu 213001,China)

机构地区：[1]常州市第三人民医院普外科,江苏常州213001

出　　处：《新中医》2024年第22期157-166,共10页New Chinese Medicine

基　　金：常州市科技计划项目(CJ20181168)。

摘　　要：目的:基于网络药理学和分子对接技术探讨槲芪散治疗原发性肝癌的作用机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)数据库获取槲芪散的活性成分,利用GeneCards、OMIM及PharmGkb数据库筛选原发性肝癌相关基因,并采用R软件获取药物-疾病交叉靶点。采用Cytoscape3.7.2软件对药物-疾病交叉靶点与活性成分进行槲芪散活性成分-靶点-原发性肝癌网络构建,筛选出核心成分。采用STRING平台对于药物-疾病交叉靶点进行蛋白质–蛋白质相互作用(PPI)网络分析,通过MCODE插件进行聚类分析以获得与原发性肝癌患者预后相关的关键靶点,并通过TCGA数据库的原发性肝癌队列对关键靶点进行预后分析。采用R语言软件包对作用靶点进行基因本体论(GO)生物功能分析和京都基因和基因组百科全书(KEGG)通路富集分析,并利用AutoDock Vina1.1.2软件对主要活性成分与关键靶点进行分子对接验证。结果:共筛选出槲芪散活性成分113个,作用靶点226个,1765个疾病靶点,预测得到116个抗原发性肝癌靶点。槲芪散治疗原发性肝癌的关键成分有槲皮素、山柰酚、木犀草素、柚皮素、丹参酮ⅡA等。PPI网络显示,雌激素受体1(ESR1)、半胱氨酶蛋白酶3(CASP3)、肿瘤蛋白53(TP53)、B细胞淋巴瘤2(BCL2)、信号转导与转录激活因子3(STAT3)、丝裂原活化蛋白激酶3(MAPK3)、细胞周期蛋白D1(CCND1)、丝裂原活化蛋白激酶1(MAPK1)、Fos原癌基因(FOS)、蛋白激酶B1(AKT1)和热休克蛋白90α家族A成员1(HSP90AA1)为槲芪散治疗原发性肝癌的关键靶点。预后分析显示,ESR1、CASP3、MAPK3、AKT1以及HSP90AA1的表达与原发性肝癌患者的生存时间密切相关。富集分析揭示,槲芪散主要富集在化学应激的细胞反应、活性氧化物的反应、脂多糖的反应以及对异物刺激的反应等细胞过程中发挥作用,能够调控磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-AKT)信号通�Objective:To explore Huqi San's mechanism of action in treating primary liver cancer based on network pharmacology and molecular docking technology.Methods:The active ingredients of Huqi San were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);primary liver cancer-related genes were screened using GeneCards,OMIM,and PharmGkb databases,and medicinals-disease cross targets were obtained using R software.Cytoscape 3.7.2 software was used to construct a network diagram of active ingredients-targets-primary liver cancer in Huqi San for medicinals-disease cross targets and active ingredients and screen out core components.The STRING platform was used for protein-protein interaction(PPI)network analysis of medicinals-disease cross targets;clustering analysis was performed with the MCODE plugin to obtain key targets related to the prognosis of primary liver cancer patients;the primary liver cancer cohorts in the TCGA database were used for the prognosis analysis of key targets.Gene Ontology(GO)-based functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the target genes using R language software package,and molecular docking validation was performed on the main active ingredients and key targets using AutoDock Vina software.Results:A total of 113 active ingredients,226 acting targets,and 1765 disease targets were screened from Huqi San,and 116 core anti-primary liver cancer targets were predicted.The key components of Huqi San in the treatment of primary liver cancer included quercetin,kaempferol,luteolin,naringenin,tanshinoneⅡA,etc.The PPI network showed that estrogen receptor 1(ESR1),caspase 3(CASP3),the tumor suppressor protein 53(TP53),B-cell lymphoma 2(BCL2),signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase 3(MAPK3),cyclin D1(CCND1),mitogen-activated protein kinase 1(MAPK1),Fos oncogene(FOS),protein kinase B1(AKT1),and heat shock protein 90αfamily A member

关 键 词：原发性肝癌 槲芪散 网络药理学 分子对接 作用机制 

分 类 号：R735.7[医药卫生—肿瘤]