基于网络药理学研究肝复方治疗肝癌的分子机制  

Molecular mechanism of Ganfufang in treatment of liver cancer based on network pharmacology

作　　者：邓天好[1] 蔡媛[2] 刘珍[2] 易钊旭[2] 赵梁[1] 张振 曾普华[1] 潘敏求[1] DENG Tianhao;CAI Yuan;LIU Zhen;YI Zhaoxu;ZHAO Liang;ZHANG Zhen;ZENG Puhua;PAN Minqiu(The Affiliated Hospital of Hunan Academy of Chinese Medicine,Changsha 410006,Hunan,China;Hunan Academy of Chinese Medicine,Changsha 410006,Hunan,China;Hunan University of Chinese Medicine,Changsha 410208,Hunan,China)

机构地区：[1]湖南省中医药研究院附属医院,湖南长沙410006 [2]湖南省中医药研究院,湖南长沙410006 [3]湖南中医药大学,湖南长沙410208

出　　处：《湖南中医杂志》2021年第3期154-160,共7页Hunan Journal of Traditional Chinese Medicine

基　　金：湖南省自然科学基金面上项目(2017JJ2169,2018JJ3310);湖南省中医药科研计划项目(2021221,201810);湖南省中医药研究院院级项目(201806);湖南省中医药研究院附属医院医院首届朝阳人才建设项目;全国中医药创新骨干人才项目(国中医药人教函[2019]128号);湖南省“121”高层次人才项目(第2018-03-027)。

摘　　要：目的:基于网络药理学方法,探究肝复方有效活性物质治疗肝癌的相关作用靶点及潜在分子机制。方法:通过检索中药系统药理学数据库与分析平台(TCMSP)及国内外文献筛选出肝复方药味中的化合物以及相关靶点蛋白。通过GeneCards数据库获取肝癌相关疾病靶点。运用Cytoscape 3.2.1软件构建"药物-有效成分-靶点"网络、蛋白相互作用(PPI)网络,并通过网络拓扑分析筛选出核心靶点。最后,通过DAVID进行基因本体(GO)和KEGG信号通路富集分析。结果:通过口服生物利用度(OB)≥30%,类药性(DL)≥0.18的筛选获得有效成分104种,药物对应的靶点1135个,肝癌相关靶点16490个;豆甾醇、人参皂苷、β-谷甾醇为主要核心成分;白细胞介素6(IL-6)、表皮生长因子受体(EGFR)、胱天蛋白酶3(CASP3)为关键靶点。结论:肝复方治疗肝癌具有多成分、多靶点、多通路的作用特点,其作用机制可能是通过IL-6、血管内皮生长因子(VEGF)A、EGFR、CASP3等核心靶点来调节,涉及VEGF、PI3K-Akt与p53等相关信号通路。本研究应用网络药理学预测肝复方治疗肝癌的分子机制,为其临床应用提供了理论依据。Objective:To investigate the targets and potential molecular mechanism of the active components of Ganfufang in the treatment of liver cancer based on network pharmacology.Methods:Traditional Chinese Medicine Systems Pharmacology and related articles in China and globally were used to screen out the compounds of the herbal medicines in Ganfufang and related target proteins.The GeneCards database was used to obtain the targets of liver cancer.Cytoscape 3.2.1 was used to construct a"drug-effective constituent-target"network and a protein-protein interaction network,and a network topology analysis was performed to screen out core targets.Finally,Database for Annotation,Visualization and Integrated Discovery was used to perform gene ontology and KEGG pathway enrichment analyses.Results:A total of 104 effective constituents were screened out based on the criteria of oral bioavailability≥30%and drug-likeness≥0.18,with 1135 corresponding targets,and there were 16490 targets associated with liver cancer.Stigmasterol,ginsenoside,andβ-sitosterol were the core constituents,and interleukin-6(IL-6),epidermal growth factor receptor(EGFR),and CASP3 were key targets.Conclusion:Ganfufang has the features of multiple constituents,targets,and pathways in the treatment of liver cancer,possibly by regulating the core targets such as IL-6,vascular endothelial growth factor A,EGFR,and CASP3,with the involvement of the VEGF,PI3 K-Akt,and p53 signaling pathways.This study predicts the molecular mechanism of Ganfufang in the treatment of liver cancer based on network pharmacology and provides a theoretical basis for clinical application.

关 键 词：肝癌 肝复方 网络药理学 PPI GO 分子机制 

分 类 号：R285.5[医药卫生—中药学]