基于网络药理学和分子对接探讨黄芪补肾活血汤治疗乳腺癌的作用机制  

Exploration into the Mechanism of Action of Huangqi Kidney-replenishing and Blood-activating Decoction in the Treatment of Breast Cancer based on Network Pharmacology and Molecular Docking

作　　者：张梦棣 梁鸿艺 时光喜[2] 李静蔚[2] ZHANG Mengdi;LIANG Hongyi;SHI Guangxi;LI Jingwei(First Clinical Medical School,College of TCM,Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学第一临床医学院,山东济南250014 [2]山东中医药大学附属医院,山东济南250014

出　　处：《西部中医药》2024年第6期61-68,共8页Western Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82374452);全国中医临床特色技术传承骨干人才项目(全国中医药人教函〔2019〕36号);山东省齐鲁卫生与健康领军人才项目(鲁卫人字〔2020〕3号)。

摘　　要：目的:基于网络药理学和分子对接预测黄芪补肾活血汤治疗乳腺癌的作用机制。方法:利用中药系统药理学数据库和分析平台(traditional Chinese medicines systems pharmacology platform,TCMSP)、BATM-TCM数据库等筛选黄芪补肾活血汤主要活性成分以及相关靶点,通过Gene Cards数据库搜索乳腺癌相关基因并进行筛选,将黄芪补肾活血汤靶点与乳腺癌基因进行映射,利用Cytoscape 3.8.2软件构建中药-成分-靶点可视化网络,绘制蛋白互作网络及进行基因本体(gene ontology,GO)、京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,筛选出核心基因。将黄芪补肾活血汤复方成分与关键靶点通过Swiss Dock网站进行分子对接验证。结果:黄芪补肾活血汤有效成分136个,潜在治疗靶点828个,其中76个是黄芪补肾活血汤治疗乳腺癌的潜在靶点。在蛋白互作网络中发现TP53、VEGFA、MAPK8、JUN、EGF等可能是黄芪补肾活血汤治疗乳腺癌的关键靶点。通过GO、KEGG富集分析发现作用机制涉及的通路包括PI3K-Akt信号通路、肿瘤中的microRNAs、RNA聚合酶Ⅱ转录因子复合物肌膜、转录因子结合、G蛋白偶联胺受体活性、血红素结合、蛋白质结构域特异性结合、核受体活性、癌症中的转录调控异常、血管内皮生长因子信号通路等。通过分子对接验证显示,化合物槲皮素、山柰酚、β-谷甾醇、木犀草素、植物甾醇与关键靶点PGR、ADRB2、NR3C2、PREE1、SCN5A具有较好的结合能力。结论:通过网络药理学构建“药物-成分-靶点-信号通路”网络及分子对接技术验证,发现黄芪补肾活血汤治疗乳腺癌主要是通过抗癌、抑制雌激素受体的表达、调节免疫等多通路、多靶点实现的,为临床治疗乳腺癌提供了更多的治疗方法,给临床用药提供了更多的选择。Objective:To predict the mechanism of action of Huangqi(Astragali radix)kidney-replenishing and blood-activating decotion in the treatment of breast cancer based on network pharmacology and molecular docking.Methods:The traditional Chinese medicines systems pharmacology platform(TCMSP)and BATM-TCM databases were used to screen the main active ingredients and related targets of Huangqi kidney-replenishing and blood-activating decotion,and the Gene Cards database was used to search and screen for breast cancer-related genes after the targets of the decoction were mapped to breast cancer-related genes.Cytoscape 3.8.2 software was used to construct the visualization network of traditional Chinese medicines-components-targets,to draw the protein interactions network,and to conduct the gene ontology(GO),Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis,so as to screen out the core genes.The compound components of the decoction and the key targets were verified by molecular docking through Swiss Dock website.Results:There were 136 active ingredients and 828 potential therapeutic targets in the decoction,of which 76 were potential targets of the decoction for the treatment of breast cancer.TP53,VEGFA,MAPK8,JUN,and EGF were found to be the possible key targets of the decoction for breast cancer treatment in the protein interactions network.The pathways involved in the mechanism of action were found by GO and KEGG enrichment analysis,including PI3K-Akt signaling pathway,microRNAs in tumors,RNA polymerase II transcription factor complex myosin,transcription factor binding,G protein-coupled amine receptor activity,heme binding,protein structural domain-specific binding,nuclear receptor activity,transcriptional regulation abnormality in cancers,vascular endothelial growth factor signaling pathway,etc.Molecular docking validation showed that the compounds quercetin,kaempferol,β-sitosterol,lignans,phytosterols have good binding ability to the key targets PGR,ADRB2,NR3C2,PREE1,SCN5A.Conclusion:Through the constru

关 键 词：乳腺癌 黄芪补肾活血汤 网络药理学 分子对接 作用机制 

分 类 号：R737.9[医药卫生—肿瘤]