基于网络药理学与分子对接的丹皮酚治疗结直肠癌的分子机制研究

Assessment of the molecular mechanism of paeonol in colorectal cancer treatment based network pharmacology and molecular docking

目的基于网络药理学与分子对接探讨丹皮酚治疗结直肠癌的靶点与作用机制。方法通过PubChem、SwissTargetPrediction和TargetNet数据库检索丹皮酚的药物靶点,使用Genecards、OMIM和TTD数据库检索结直肠癌的疾病靶点,通过Venny在线工具获得交集靶点。利用Metascape数据库完成交集靶点的基因本体(GO)功能富集分析和京都基因与基因组数据库(KEGG)信号通路富集分析。交集靶点经STRING数据库与Cytoscape软件分析其相互作用关系并筛选枢纽节点。采用LeDock与CB-Dock2软件完成丹皮酚与枢纽节点的分子对接,以筛选丹皮酚的核心药物靶点。结果经筛选得到21个药物靶点。富集分析结果显示,丹皮酚发挥作用的分子机制涉及癌症通路、Ras信号和Rap1信号等通路,而其涉及的生物过程包括细胞对缺氧的反应以及调控激酶活性等。蛋白质-蛋白质相互作用分析发现9个靶点为蛋白质相互作用的枢纽。分子对接结果显示,丹皮酚和枢纽节点中的SRC、EP300、MMP9具有最高亲和力,提示SRC、EP300以及MMP9可能是丹皮酚治疗结直肠癌的核心靶点。结论丹皮酚可能通过靶向SRC、EP300与MMP9,调控Ras、Rap1等信号通路与激酶活性等生物过程,进而发挥治疗结直肠癌的作用。

Objective To elucidate the targets and mechanisms of action of paeonol in the treatment of colorectal cancer.Methods Drug targets for paeonol were searched using the PubChem,SwissTargetPrediction,and TargetNet databases.Targets for colorectal cancer were identified using the Genecards,OMIM,and TTD databases.To obtain the shared targets,the data were integrated using Venny.GO functional enrichment analysis and KEGG signaling pathway enrichment analysis were completed using Metascape.The STRING database and Cytoscape software were used to analyze the interactions and screen for hub nodes.Subsequently,LeDock and CB-Dock2 software were employed to perform molecular docking for clarifying the core drug target of paeonol.Results Twenty-one drug targets were selected.The enrichment analysis results revealed that paeonol’s mechanisms of action were associated with pathways such as cancer pathways,Ras signaling,and Rap1 signaling.The biological processes included cellular response to hypoxia,regulation of kinase activity,and others.The interaction analysis revealed that nine drug targets acted as hub nodes.The molecular docking results indicated that SRC,EP300,MMP9,among the hub nodes,exhibited the highest affinity with paeonol.This implies that SRC,EP300,and MMP9 may serve as the core targets of paeonol in the treatment of colorectal cancer.Conclusion Paeonol may exert a therapeutic effect on colorectal cancer by targeting SRC,EP300,and MMP9,subsequently regulating biological processes such as kinase activities and signaling pathways such as Ras and Rap1.