基于网络药理学探讨丹参治疗结直肠癌的作用机制

Investigating the action mechanism of Danshen on colorectal cancer based on network pharmacology

目的:基于网络药理学方法探讨丹参治疗结直肠癌的作用机制,为临床的合理使用及细胞实验提供依据。方法:通过中药系统药理学数据库与分析平台(TCMSP)获取丹参的主要化学成分及其对应靶点;通过GeneCards数据库获取结直肠癌的疾病靶点;利用R软件中的Venn工具获取共同靶点。利用Cytoscape 3.7.2构建“有效成分-核心靶点-结直肠癌基因”网络图。通过String平台构建蛋白质-蛋白质相互作用网络图,分析蛋白质之间的相互作用。采用Bioconductor平台进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,筛选关键靶点及重要通路。结果:丹参治疗结直肠癌的主要活性成分为木犀草素、丹参酮ⅡA、隐丹参酮、丹参新醌、甲酰丹参酮,关键靶点包括丝氨酸/苏氨酸蛋白激酶1(Serine/threonine Protein Kinase 1,AKT1)、白细胞介素(Interleukin,IL)-6、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)等,主要参与的生物过程为DNA-转录因子结合、核受体活性、配体激活转录因子活性等,主要富集的重要通路有PI3K-Akt信号通路、肿瘤坏死因子信号通路、IL-17信号通路等。结论:本研究初步揭示丹参治疗结直肠的分子及细胞通路机制,为临床使用提供了一定的科学依据,为后续的细胞实验提供了参考方向。

Objective:To explore the action mechanism of Danshen(salvia miltiorrhiza)on colorectal cancer based on network pharmacology then to provide a basis for its clinically rational application and cell experiments.Methods:The main chemical components and corresponding targets of Danshen were obtained by TCMSP.The disease targets of colorectal cancer were obtained through GeneCards database.Venn tool in R software was used to obtain common targets.Cytoscape 3.7.2 was used to construct“active ingredient-core target-colorectal cancer gene”network diagram.The PPI network was constructed by String platform for PPI analysis.Bioconductor platform was used to execute GO enrichment analysis and KEGG pathway enrichment analysis in order to screen out key targets and important pathways.Results:The main active components of Danshen on colorectal cancer were luteolin,tanshinone IIA,cryptotanshinone,danshenxinquinone and formyl tanshinone.The key targets included AKT1,IL-6,EGFR,VEGFA and so on.The main biological processes involved DNA binding transcription factor binding,nuclear receptor activity,ligand-activated transcription factor activity,etc.The main enrichment pathways included PI3K-Akt signaling pathway,TNF signaling pathway,IL-17 signaling pathway,etc..Conclusion:In this study,the molecular and cellular pathway mechanism of Danshen on of colorectal cancer was preliminarily revealed,which provides a certain scientific basis for its clinical application and a reference direction for subsequent cell experiments.