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本研究依托网络药理学，从多靶点、多途径的角度分析白藜芦醇(resveratrol, RES)治疗结肠癌的潜在机制。从Swiss Target Prediction、 TCMSP、 UniProt、 OMIM、 GeneCards和PubChem数据库中获取白藜芦醇治疗结肠癌的目标基因，使用Venn 2.1.0确定交集基因。通过STRING数据库构建蛋白质相互作用(protein-protein interaction, PPI)网络。使用Cytoscape软件对PPI网络相互作用进行拓扑分析。使用R程序包进行GO和KEGG富集分析，并筛选出相关信号通路。使用Autodock Vina软件进行分子对接分析。随后通过RT-qPCR、 Western blot和划痕实验进行体外验证。筛选得到白藜芦醇治疗结肠癌的潜在靶点152个，通过CytoHubba分析得到10个关键基因。GO富集分析显示，细胞膜是生物过程发生的主要场所。KEGG结果表明，PI3K/AKT是白藜芦醇治疗结肠癌的关键信号通路。分子对接结果显示白藜芦醇与关键靶蛋白之间结合力良好。RT-qPCR结果显示，白藜芦醇对关键基因起到了相应的调节作用。Western blot结果显示，白藜芦醇可以下调HT-29结肠癌细胞模型PI3K/AKT通路的表达。划痕实验显示，HT-29细胞的迁移受到白藜芦醇的抑制。本研究表明白藜芦醇可以通过多个靶点和途径发挥抗结肠癌作用，也显示了网络药理学在药物研究中的潜力。
Abstract：This study analyzed the potential mechanism of resveratrol(RES) on anti-colon cancer from a multi-target and multi-pathway perspective based on network pharmacology. Target genes for RES and colon cancer were searched from Swiss Target Prediction, TCMSP, UniProt, OMIM, GeneCards, and PubChem databases, then intersection genes were identified using Venn 2.1.0. Protein-protein interaction(PPI) network was constructed by STRING database. Topological analysis of PPI network interactions was performed using Cytoscape. GO and KEGG enrichment analysis was performed using the R program package. Molecular docking analysis was performed by Autodock Vina. In vitro validation was performed by RT-qPCR, Western blot and scratch assay. 152 potential targets for RES in the treatment of colon cancer were obtained, and 10 key genes were obtained by CytoHubba analysis. GO enrichment analysis showed that the cell membrane was the main site where the biological process occurred. KEGG results indicated that PI3K/AKT was a key signaling pathway. Molecular docking results showed good binding between RES and key target proteins. RT-qPCR results showed that RES regulated the expression of key genes. Western blot results showed that RES downregulated the expression of PI3K/AKT pathway in HT-29 colon cancer cell model. Scratch assay showed that the migration of HT-29 cells was inhibited by RES. This study shows that RES exert anti-colon cancer effect through multiple targets and pathways.
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基本信息:
DOI：10.13417/j.gab.042.001223
中图分类号:R285
引用信息:
[1]王珍,黄俊,韦镔倩,等.基于网络药理学探讨白藜芦醇治疗结肠癌的潜在机制[J].基因组学与应用生物学,2023,42(11):1223-1234.DOI:10.13417/j.gab.042.001223.
基金信息:
国家自然科学基金项目(81660093)资助
2023-04-06
2023-04-06
2023-04-06