黄芪-莪术药对基于网络药理学的抗大肠癌分子机制

目的:运用计算机网络药理学技术预测黄芪-莪术药对治疗大肠癌的作用靶点和信号通路,进一步分析其抗大肠癌物质基础和作用机制。方法:通过Therapetutic Target Database(TTD),Drugbank数据库收集大肠癌疾病作用靶点;从中药系统药理学分析平台(TCMSP)获得黄芪、莪术所含中药成分;运用Chem Mapper,Pharm Mapper数据库预测所选中药成分作用的疾病靶点;采用Cytoscape软件建立"化合物-疾病靶点"网络模型;利用Clue GO插件对靶点进行基因功能(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。结果:黄芪-莪术药对活性化合物-大肠癌疾病靶点网络包含56个化合物和54个靶点,关键靶点涉及AMP激活蛋白激酶α1(PRKAA1),前列腺素内过氧化物合酶1(PTGS1),环氧化酶2(PTGS2),胸苷酸合成酶(TYMS),肝羧酯酶1(CES1),血管内皮生长因子B(VEGFB),血管内皮生长因子A(VEGFA),谷胱甘肽S-转移酶P(GSTP1),丝氨酸羟甲基转移酶(gly A)等;靶点的基因功能偏向于肽基酪氨酸的磷酸化,调节细胞外调节蛋白激酶(ERK) 1和ERK2信号串联,内皮细胞凋亡过程的负调节等;重要的KEGG通路涉及癌症通路,Ras信号通路,Rap1信号通路,磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路等。结论:黄芪-莪术药对通过抑制肿瘤细胞增殖分化、促进肿瘤细胞凋亡、抗肿瘤新生血管生成以及增强机体免疫的多表型干预的网络模式产生抗大肠癌活性,其作用信号通路与Ras信号通路,Rap1信号通路,PI3K/Akt信号通路最为相关。

Anti-colorectal Cancer Molecular Mechanism of Astragali Radix and Curcumae Rhizoma Based on Network Pharmacology

Objective:The network pharmacology method was used to predict targets and signaling pathways of the drug pair Astragali Radix and Curcumae Rhizoma in treating colorectal cancer,in order to analyze the effective material basis and action mechanism. Method:Disease targets for colorectal cancer were collected through Therapetutic Target Database(TTD)and Drugbank database. Components of Astragali Radix and Curcumae Rhizoma were obtained from the Traditional Chinese Medicine Systems Pharmacology Database, and the Analysis Platform (TCMSP). ChemMapper and PharmMapper database were used to predict the disease targets of effective components. The "compound-disease targets" network model was established by Cytoscape software. The function analysis of gene ontology(GO)and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG)were carried out with ClueGO plug-in. Result:The network contained 56 compounds and 54 targets. The crucial targets included 5''-AMP-activated protein kinase catalytic subunit alpha1(PRKAA1), prostaglandin G/H synthase 1(PTGS1), prostaglandin G/H synthase 2(PTGS2), Thymidylate synthase(TYMS), Carboxylesterase 1(CES1), vascular endothelial growth factor B(VEGFB), vascular endothelial growth factor A(VEGFA), glutathione S-transferase P(GSTP1), and serine hydroxymethyltransferase 1(glyA). Function about target genes inclined to peptide-tyrosine phosphorylation, extracellular regulated protein kinase(ERK)1 and ERK2 signal series, negative regulation of endothelial cell apoptosis process, et al. Important KEGG Pathways involved pathways in cancer, Ras signaling pathways, Rap1 signaling pathways, and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways. Conclusion:The anti-colorectal cancer activities of Astragali Radix and Curcumae Rhizoma were mainly affected by inhibiting cell proliferation and differentiation, promoting tumor cell apoptosis, resisting tumor angiogenesis, and enhancing immunity as phenotype intervention mode in network. The active signaling pathway is most related to Ras signaling pathway, Rap1 signaling pathway and PI3K/Akt signaling pathway.