基于网络药理学和生物信息学探讨小柴胡汤治疗肝细胞癌的作用机制

Study on the mechanism of Xiaochaihu Decoction in the treatment ofhepatocellular carcinoma based on network pharmacology and bioinformatics

目的采用TCGA数据挖掘和网络药理学方法分析小柴胡汤治疗肝细胞癌(HCC)的药效物质基础及药理机制。方法通过TCGA数据库挖掘HCC差异表达基因、通过TCMID、TCMSP数据库和文献检索得到小柴胡汤的活性成分及其作用靶点;绘制韦恩图获得小柴胡汤-HCC共有靶点。通过Cytoscape软件构建疾病-药物-有效成分-靶点相互作用网络;利用R软件对共有靶点进行GO功能注释和KEGG通路富集分析。结果共获得HCC差异表达基因4880个,小柴胡汤治疗HCC潜在有效成分142个,包括槲皮素、山柰酚、黄芩素、汉黄芩素等,这些有效成分共作用于242个靶点,其中有100个与HCC相关,其潜在调控信号通路61条,包括IL-17、TNF、HIF-1等与癌细胞生长和凋亡密切相关的信号通路。结论小柴胡汤可能通过多成分、多靶点、多途径的方式发挥治疗HCC的作用,为其临床应用提供科学依据,也为经典方剂的防病治病机制研究提供参考思路。

Objective To analyze the mechanisms of Xiaochaihu Decoction in the treatment of hepatocellular carcinoma(HCC)based on TCGA data mining and network pharmacology.Methods The differentially expressed genes of HCC were mined from TCGA database,the active components and targets of Xiaochaihu Decoction were obtained by TCMID and TCMSP database as well as literature mining,and the disease-drug common target was obtained by Venn map.The disease-drug-active component-target interaction network was constructed by Cytoscape software,while the GO function annotation and KEGG pathway enrichment analysis were carried out by R software.Results A total of 4880 differentially expressed genes of HCC were obtained.There were 142 potential active components of Xiaochaihu Decoction in treating HCC,including quercetin,kaempferol,baicalin and wogonin,etc.These active components acted on 242 targets,100 of which were related to HCC.There were 61 potential regulatory signaling pathways which were closely related to the growth and apoptosis of cancer cells,including IL-17,TNF,HIF-1,etc.Conclusion Xiaochaihu Decoction may play a role in the treatment of HCC through multi-components,multi-targets and multi-ways.It not only provides a scientific basis for its clinical application,but also provides a reference for the study of mechanism of prevention and treatment of classical prescriptions.