基于网络药理学解析紫花牡荆素治疗结直肠癌的分子机制

Dissecting the Molecular Mechanism of Casticin in the Treatment of Colorectal Cancer Based on Network Pharmacology

目的基于网络药理学解析紫花牡荆素治疗结直肠癌的分子机制,为紫花牡荆素治疗结直肠癌提供潜在作用靶点和新思路。方法在Pubchem数据库以及药物靶点预测数据库SwissTarget Prediction获取紫花牡荆素相关潜在作用靶点,借助人类孟德尔遗传病数据库(OMIM)平台检索结直肠癌相关靶点,并将其与紫花牡荆素相关潜在作用靶点在Venny数据库相互映射获得共同靶点;运用STRING数据库构建紫花牡荆素-结直肠癌共同靶点蛋白质-蛋白质相互作用(PPI)网络图;利用DAVID数据库对紫花牡荆素治疗结直肠癌靶点进行基因本体(GO)功能注释和京都基因与基因百科全书(KEGG)通路富集分析,并使用Cytoscape 3.8.2软件构建紫花牡荆素通路网络图;利用微生信在线网站绘制KEGG气泡图;通过对紫花牡荆素和关键靶点进行分子对接验证。结果预测结果显示紫花牡荆素和结直肠癌中的靶点取交集后获得6个共同靶点,其中关键靶点2个,分别是络氨酸蛋白激酶(SRC)和丝氨酸蛋白激酶(ATK1)。GO富集分析涉及生物过程35个、细胞组分2个、分子功能8个。KEGG通路富集筛选得到28个相关通路,主要作用于Erb-b受体酪氨酸激酶(ErbB)、雌激素(Estrogen)等信号通路。分子对接结果表明紫花牡荆素能够与SRC、AKT1结合,且有较强的亲和力。结论紫花牡荆素可能直接靶向SRC,调控ErbB通路,从而发挥治疗结直肠癌的作用。

Objective To analyze the molecular mechanism of casticin in the treatment of colorectal cancer based on network pharmacology,and to provide potential targets and new ideas for casticin in the treatment of colorectal cancer.Methods The potential targets related to casticin officinale were obtained from the Pubchem database and the drug target prediction database SwissTarget Prediction,and the colorectal cancer-related targets were retrieved with the help of the Human Mendelian Inherited Diseases Database(OMIM)platform.and the mutual mapping of these two types of targets in the Venny database resulted in the acquisition of common targets.The protein-protein interaction(PPI)network map of the common target of casticin officinale and colorectal cancer was constructed using the STRING database.The gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genes(KEGG)pathway enrichment analysis of the target of casticin officinale for colorectal cancer were performed using the DAVID database,and the network map of the purpureol pathway was constructed using Cytoscape 3.8.2 software.The KEGG bubble chart was mapped using the Microbiology Online website.Molecular docking verification of casticin officinale and key targets was carried out.Results The prediction results showed that six common targets were obtained after the intersection of casticin officinale and and the targets in colorectal cancer,of which two were key targets,namely,Tyrosine-protein kinase SRC(SRC)and Serinelthreonine-protein kinase AKT.GO enrichment analysis involved 35 biological processes,2 cellular components,and 8 molecular functions.28 related pathways were obtained from KEGG pathway enrichment screening,mainly acting on Erb-b receptor tyrosine kinase(ErbB),Estrogen and other signaling pathways.The results of molecular docking showed that casticinin could bind to SRC and AKT1 with strong affinity.Conclusion Casticin officin may directly target SRC and regulate ErbB pathway,thus playing a role in the treatment of colorectal cancer.