基于网络药理学探讨健脾益胃祛邪方治疗大肠癌作用机制
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R285

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珠海市医学科研基金项目(2220009000293)


Mechanism of Jianpi Yiwei Quxie Prescription in Treating Colorectal Cancer Based on Network Pharmacology
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    摘要:

    目的:基于网络药理学研究方法探讨健脾益胃祛邪方治疗大肠癌的作用机制。方法:应用中药系 统药理学平台和中药分子机制生物信息学分析工具筛选健脾益胃祛邪方的活性成分及其靶点。利用药物靶标数 据库、比较毒理基因组学数据库、在线人类孟德尔遗传数据库以及GeneCards数据库检索大肠癌的靶点。通过 Venny2.1平台得出健脾益胃祛邪方和大肠癌的共同靶点,绘制韦恩图。将健脾益胃祛邪方与大肠癌的共同靶点 录入STRING数据库中进行分析,构建大肠癌和健脾益胃祛邪方的蛋白质-蛋白质相互作用(PPI) 网络。借助 DAVID数据库,对健脾益胃祛邪方与大肠癌的共同靶点进行基因本体(GO) 功能富集分析以及京都基因与基 因组百科全书(KEGG) 通路富集分析。利用Cytoscape3.82软件构建“药物-成分-作用靶点-通路-疾病”网络 模型。结果:通过筛选,得到126个健脾益胃祛邪方的主要活性成分,1 014个与大肠癌相关的人类靶点, 59 个健脾益胃祛邪方与大肠癌的共同靶点。PPI网络分析提示前列腺素内过氧化物合酶1、核受体辅活化因 子2、雄激素受体、热休克蛋白90α、雌激素受体1、胰蛋白酶-1、过氧化物酶体增殖物激活受体γ、丝氨酸/苏 氨酸激酶β、雌激素受体2、丝氨酸/苏氨酸蛋白激酶Chk1是健脾益胃祛邪方治疗大肠癌的核心靶点。GO功能 富集分析得到1 133项生物过程条目,93项分子功能条目,27项细胞组分条目;KEGG通路富集分析共得到 140条信号通路。健脾益胃祛邪方的主要活性成分如槲皮素、山奈酚、木犀草素、汉黄芩素等,通过靶向调控 机制与化学致癌-受体激活、细胞凋亡、结直肠癌、p53信号通路、人巨细胞病毒感染以及内分泌抵抗等信号 通路,发挥治疗大肠癌的作用。结论:健脾益胃祛邪方治疗大肠癌具有多成分、多靶点、多通路的特点。

    Abstract:

    Abstract:Objective:To explore the mechanism of Jianpi Yiwei Quxie Prescription in the treatment of colorectal cancer based on network pharmacology. Methods:The active components and targets of Jianpi Yiwei Quxie Prescription were screened by the function of bioinformatics analysis in Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and A Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM). The targets of colorectal cancer were searched through Therapeutic Target Database, Comparative Toxicogenomics Database, Online Mendelian Inheritance in Man and GeneCards databases. The common targets of Jianpi Yiwei Quxie Prescription and colorectal cancer were obtained via Venn 2.1, and Venny diagram was drawn. The common targets were analyzed through STRING database, and then the protein-protein interaction (PPI) network of colorectal cancer and Jianpi Yiwei Quxie Prescription was constructed. With the use of David database, Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the common targets of Jianpi Yiwei Quxie Prescription and colorectal cancer. Cytoscape3.82 software was used to construct a “drugcomponent- target-pathway-disease” network model. Results: Through screening, 126 main active components of Jianpi Yiwei Quxie Prescription , 1 014 human targets related to colorectal cancer, and 59 common targets of Jianpi Yiwei Quxie Prescription and colorectal cancer were obtained. PPI network analysis showed that prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator 2, androgen receptor, heat shock proteins 90α, estrogen receptor 1, trypsin-1, peroxisome proliferators-activated receptors γ, receptor serine/threonine kinases β, estrogen receptor 2 and checkpoint kinase 1 were the core targets of Jianpi Yiwei Quxie Prescription. A total of 1 133 biological process items, 93 molecular function items and 27 cellular component items were obtained by GO functional enrichment analysis of potential targets, and 140 signaling pathways were obtained by KEGG pathway enrichment analysis. The main active compounds, like quercetin, kaempferol, luteolin and scutellarin, played a role in the treatment of colorectal cancer by targeting regulatory mechanisms and chemical carcinogenic-receptor activation, cell apoptosis, colorectal cancer, p53 signaling pathway, human cytomegalovirus infection, endocrine resistance and other signaling pathways. Conclusion: Jianpi Yiwei Quxie Prescription has the characteristics of multiple components,multiple targets and multiple pathways.

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姜亚君,蔡德珺,梁学敏,朱建红.基于网络药理学探讨健脾益胃祛邪方治疗大肠癌作用机制[J].新中医,2024,56(23):146-153

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  • 在线发布日期: 2024-12-19
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