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目的:应用分子对接和网络药理学方法,预测绞股蓝-半枝莲药对防治大肠癌的潜在靶点及信号通路。方法:通过TCMSP数据库检索绞股蓝-半枝莲的主要活性化合物,并筛选出两味中药活性成分的作用靶点;借助GeneCards、TTD、CTD数据库获取大肠癌的相关靶标。利用STRING数据库和Cytoscape3.6.1软件构建药物-化合物-靶点网络、靶蛋白互作PPI网络。采用DAVID数据库对核心靶点进行GO富集和KEGG通路注释分析。借助AutoDock进行分子对接。结果:根据筛选条件得到绞股蓝-半枝莲药对15个活性化合物和116个药物靶点,与大肠癌相关靶点49个,通过GO分析得出36个生物过程(BP,biological process)、11个细胞组分(CC,cellular component)、16个分子功能(MF,molecular function),通过KEGG通路富集分析得出67条信号通路。结论:本研究从分子对接和网络药理学层面初步揭示绞股蓝-半枝莲药对的活性化合物通过多成分、多靶点、多通路防治大肠癌,其分子机制与可能TP53、JUN、MAPK1、HSP90AA1、EGF、IL6、EGFR、PTGS2等信号相关,涉及癌症信号通路、HIF-1信号通路、胰腺癌、PI3K-Akt信号通路、炎症性肠病、结直肠癌、癌症中的MicroRNA、p53信号通路等,为后续多靶点药物研发、分子生物学实验及相关临床研究奠定理论基础。
Abstract：Objective:To apply molecular docking and network pharmacology methods to predict the potential targets and signaling pathways of Gynostemma pentaphyllum-Scutellaria barbata drugs against colorectal cancer. Methods:The main active compounds of Gynostemma pentaphyllum-Scutellaria barbata were searched through the TCMSP database,and the targets of the active ingredients of the two flavors of traditional Chinese medicine were screened;the relevant targets of colorectal cancer were obtained with the help of GeneCards,TTD,and CTD databases. The STRING database and Cytoscape 3.6.1 software were used to construct the drug-compound-target network and target protein interaction PPI network. The DAVID database was used to perform GO enrichment and KEGG pathway annotation analysis on core targets. Use AutoDock for molecular docking.Results:According to the screening conditions,15 active compounds and 116 drug targets of Gynostemma pentaphyllum and Scutellaria barbata were obtained,and 49 targets related to colorectal cancer. 36 biological processes(BP)and 11 biologic processes were obtained by GO analysis. Cellular components(CC,cellular component),16 molecular functions(MF,molecular function),67 signal pathways were obtained through enrichment analysis of KEGG pathway.Conclusion:This study initially revealed that the active compounds of Gynostemma pentaphyllum-Scutellaria barbata pair through multiple components,multiple targets,and multiple pathways in preventing and treating colorectal cancer through molecular docking and network pharmacology. The molecular mechanisms and possible TP53,JUN,MAPK1,HSP90 AA1 EGF,IL6,EGFR,PTGS2 and other signals are related to cancer signaling pathway,HIF-1 signaling pathway,pancreatic cancer,PI3 K-Akt signaling pathway,inflammatory bowel disease,colorectal cancer,MicroRNA in cancer,p53 signaling pathway,etc. It will lay a theoretical foundation for the follow-up multi-target drug development,molecular biology experiments and related clinical research.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20200529.002
中图分类号:R285
引用信息:
[1]赖冬萍,张涛,廖美华,等.基于分子对接和网络药理学探讨绞股蓝-半枝莲药对防治大肠癌的作用机制[J].海南医学院学报,2021,27(06):442-451.DOI:10.13210/j.cnki.jhmu.20200529.002.
基金信息:
国家自然科学基金项目（81260536）; 广西自然科学基金项目（2018GXNSFAA281042）; 广西中医药大学一流学科项目（2018XK082,2019XK164）~~
2020-05-29
2020-05-29
2020-05-29