基于网络药理学探讨柴胡对4种分子分型乳腺癌的治疗机制

Mechanism of Bupleuri Radix in Treatment of Four Molecular Types of Breast Cancer Based on Network Pharmacology

目的:基于网络药理学探究柴胡对4种分子分型乳腺癌的治疗机制。方法:应用中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID),获取柴胡的药物靶标,应用GeneCards和人类孟德尔遗传数据库(OMIM)获取4种分子分型乳腺癌的疾病靶标,将二者靶标进行网络分析,应用STRING平台构建蛋白质-蛋白质相互作用(PPI)网络,通过Cytoscape软件统计靶标的关联频次。应用R语言软件对公共交集及非公共交集靶标进行基因本体(GO)富集分析。应用DAVID平台对公共交集及非公共交集靶标进行京都基因和基因组百科全书(KEGG)富集分析,通过Cytoscape软件将结果制成网络图。结果:交集的靶标共101个,其分子功能主要包括:RNA聚合酶Ⅱ转录因子结合、泛素-蛋白质连接酶结合、激酶调节活性等。其参与通路主要包括:MAPK信号通路、P53信号通路、VEGF信号通路等。结论:柴胡治疗4种分子分型乳腺癌是多靶标、多信号通路共同作用的过程。对于4种分子分型乳腺癌,其机制多与调节肿瘤细胞的增殖、凋亡、转移相关。

Objective:To explore the mechanism of Bupleuri Radix in the treatment of four molecular types of breast cancer based on network pharmacology.Methods:The active components and targets of Bupleuri Radix were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Traditional Chinese Medicine Integrated Database(TCMID).The targets of four molecular types of breast cancer were retrieved from Genecards and OMIM.The common targets shared by the active components and breast cancer were identified and imported into STRING for the establishment of the protein-protein interaction(PPI)network.The frequency of association of the targets was counted in Cytoscape.The gene ontology(GO)annotation of the common targets was conducted in R studio.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment of the target genes was carried out with DAVID.The results were expressed as network diagram by Cytoscape.Results:The active components of Bupleuri Radix and breast cancer shared 101 common targets,which were mainly involved in RNA polymeraseⅡtranscription factor binding,ubiquitin-like protein ligase binding,kinase regulatory activity,etc.The enriched pathways include MAPK,P53,and VEGF signaling pathways.Conclusion:Bupleuri Radix treats four molecular types of breast cancer through multiple targets and multiple signaling pathways,which may be related to the regulation of the proliferation,apoptosis,and metastasis of tumor cells.