基于网络药理学探讨阴阳攻积丸治疗肝细胞癌的潜在作用机制  

Mechanism of Yin Yang Gong Ji pill in treatment of hepatocellular carcinoma based on network pharmacology

作　　者：李玉洁 陈燕[1] 杨宏志 李永伟[1] 李跃[1] 张炯善[1] 邹增城 LI Yu-jie;CHEN Yan;YANG Hong-zhi;LI Yong-wei(The Third Affiliated Hospital,Sun Yat-Sen University(Guangzhou,510630),China)

机构地区：[1]中山大学附属第三医院,广东广州510630

出　　处：《中西医结合肝病杂志》2021年第9期828-834,共7页Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases

基　　金：广东省中医药局面上项目(No.20201054)。

摘　　要：目的:运用网络药理学方法探讨阴阳攻积丸治疗肝细胞癌(HCC)的潜在作用机制。方法:利用中药系统药理数据库和分析平台(TCMSP)获取阴阳攻积丸的有效活性成分及其作用靶点,并筛选口服利用度(OB)≥30%和类药性(DL)≥0.18的化学成分;通过检索Gene Cards数据库,人类孟德尔遗传数据库(OMIM)获取HCC疾病相关的靶点,并与药物靶点取交集,筛选得到阴阳攻积丸治疗HCC的潜在作用靶点;使用STRING数据库进行靶点信息的注释,构建蛋白互作(PPI)网络;利用Cytoscape 3.6软件构建阴阳攻积丸成分-靶点-疾病网络;采用DAVID 6.8数据库对相关潜在作用靶点进行GO分析和KEGG通路富集分析。结果:得到阴阳攻积丸的188个有效活性成分,作用于肝癌的潜在靶点110个,并预测IL-6、VEGFA、EGFR、CASP3、MAPK8、MYC、CCND1可能是阴阳攻积丸治疗肝癌的核心靶点;GO富集分析确定了123个条目,影响细胞的凋亡、核受体活性和基因转录等过程;KEGG通路富集分析明确了116条信号通路,有肝炎(Hepatitis B),PI3K-Akt信号通路,TNF信号通路,MAPK信号通路和P53信号通路等。结论:网络药理学研究结果展现了阴阳攻积丸抗HCC的多成分、多靶点、多途径的作用特点,为其潜在作用机制研究提供了理论基础。Objective:To study the potential mechanism of Yin Yang Gong Ji Pill(YYGJ)in the treatment of hepatocellular carcinoma(HCC)by using network pharmacology.Methods:The effective active components of Yin Yang Gong Ji Pill and their targets were obtained by using the traditional Chinese medicine systematic pharmacology database and analysis platform(TCMSP),and the compounds were screened with the thresholds of oral availability(OB)≥30%and drug-like(DL)≥0.18.Next,the targets related to HCC disease were screened through GeneCards and OMIM databases.Meanwhile,the interactive targets of YYGJ and HCC were acquired.Then,the target information was annotated with STRING database,and the protein interaction(PPI)network was constructed.Cytoscape 3.6 software was used to construct the component-target-disease network of YYGJ.Gene Ontology(GO)analysis and KEGG pathway enrichment analysis of interactive targets were performed using DAVID 6.8 database.Results:The 188 active components of YYGJ were obtained,involving 110 targets related to HCC.It was predicted that IL6,VEGFA,EGFR,CASP3,MAPK8,MYC,and CCND1 might be the core targets of YYGJ in the treatment of HCC.A total of 123 enrichment results were obtained by GO analysis,mainly involving cell apoptosis、nuclear receptor activity and gene transcription,etc.Meanwhile,the selected targets were enriched by KEGG analysis and it indicated that 116 signaling pathways play an important role in HCC,primarily including Hepatitis B,PI3K-Akt signaling pathway,TNF signaling pathway,MAPK signaling pathway,and p53 signaling pathway etc.Conclusion:The therapeutic effect of YYGJ with multi-compounds,multi-targets,and multi-pathways in the treatment of HCC were revealed by network pharmacology,which provides a theoretical basis for the study of its potential action mechanism.

关 键 词：肝细胞癌 阴阳攻积丸 网络药理学 

分 类 号：R735.7[医药卫生—肿瘤]