基于网络药理学的干姜抗肿瘤转移作用机制分析

Anti-tumor Metastasis Mechanism of Zingiberis Rhizoma based on Network Pharmacology

目的:采用网络药理学方法探究中药干姜的主要活性成分及其抗肿瘤转移作用机制。方法:在中药系统药理学分析平台(TCMSP)数据库中检索干姜的化学成分,根据"类药五原则"与"口服生物利用度"≥30%这一标准筛选干姜的活性成分,预测其活性成分对应的作用靶点,采用Cytoscape 3.2.1软件构建活性成分-预测靶点网络图。在Genecards数据库中以"anti-tumor metastasis"为关键词搜索抗肿瘤转移靶点,与干姜靶点映射筛选出共同靶点作为干姜的抗肿瘤转移靶点。将干姜抗肿瘤转移靶点导入STRING数据库中进行蛋白质-蛋白质相互作用分析,构建靶蛋白相互作用网络图(PPI),利用Cytoscape 3.2.1的"CytoNCA"插件筛选干姜的抗肿瘤转移核心靶点。使用DAVID数据库及Cytoscape 3.2.1的"GlueGO"插件对干姜抗肿瘤转移靶点进行KEGG信号通路富集分析和GO生物过程富集分析。结果:获得干姜中具有类药性、口服吸收良好的活性成分52种,对应靶点101个。其中抗肿瘤转移靶点40个,核心靶点10个。KEGG富集分析得到与干姜抗转移作用有关的信号通路62条,主要涉及TNF信号通路、VEGF信号通路等。GO富集分析得出与干姜抗转移作用有关的生物过程45个,主要涉及低氧反应、活性氧代谢过程等。结论:本研究初步揭示了干姜的药效物质基础及其可能的抗肿瘤转移作用机制,可为干姜抗肿瘤研究提供参考。

Objective:To explore the active components and the anti-tumor metastasis mechanism of Zingiberis Rhizoma by network pharmacology.Methods:The chemical constituents of Zingiberis Rhizoma were searched through the Chinese Medicine System Pharmacology(TCMSP)database.The active components of Zingiberis Rhizoma were screened with "Lipinski rule" and "Oral Bioavailability≥30%" rules,the targets of above components were predicted and Cytoscape 3.2.1 was used to build a network between components and targets.In Genecards database,"anti-tumor metastasis" was used as the key word to search for anti-tumor metastasis targets,and the common target was selected as the anti-tumor metastasis target by mapping with Zingiberis Rhizoma.The anti-tumor metastasis targets of Zingiberis Rhizoma were imported into a STRING database for protein-protein interaction analysis,the target protein interaction network diagram(PPI)was constructed."CytoNCA" plug-in unit in Cytoscape 3.2.1 was used to screen the key anti-tumor metastasis targets of Zingiberis Rhizoma.DAVID database and"ClueGO" plug-in unit in Cytoscape 3.2.1 were used to perform KEGG pathway enrichment analysis and GO biological process enrichment analysis.Results:Fifty-two components of Zingiberis Rhizoma were obtained and corresponding to 101 targets.Among them,there were 40 targets with anti-tumor metastasis effects and 10 key anti-tumor metastasis targets.KEGG signaling pathway analysis obtained 62 signaling pathways related to the anti-metastasis effect of Zingiberis Rhizoma,mainly related to TNF signaling pathway and VEGF signaling pathway,etc.GO biological process enrichment analysis obtained 45 biological processes related to the anti-metastasis effect of Zingiberis Rhizoma,mainly involved in response to hypoxia,reactive oxygen species metabolic process,etc.Conclusion:This study preliminarily reveals the pharmacodynamic substance basis of Zingiberis Rhizoma and its possible anti-tumor metastasis pharmacological effects mechanism,and provides basis for anti-tumor research of Zingiberis Rhizoma.