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基于网络药理学和WGCNA探讨淫羊藿治疗前列腺癌的分子机制

To explore the molecular mechanism of Epimedium in the treatment of prostate cancer based on network pharmacology and WGCNA
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摘要 目的基于网络药理学和WGCNA方法探讨淫羊藿治疗前列腺癌的潜在作用靶点,以期为前列腺癌的临床治疗提供理论依据。方法借助TCMSP、ETCM数据库和2020版药典获得淫羊藿活性成分及其对应靶点基因;R语言对数据集GSE46602进行差异分析,WGCNA筛选出前列腺癌关键基因,获得淫羊藿前列腺癌交集靶点基因;进一步进行GO和KEGG通路富集分析,STRING及Cytoscape软件构建蛋白质相互作用网络、药物活性成分靶点通路疾病网络;UALCAN网站及GEPIA数据库验证关键基因与Gleason分级的相关性并进行验证。结果淫羊藿有效活性成分31个,对应靶点基因228个,淫羊藿抗前列腺癌的潜在作用靶点9个;GO分析显示疾病交集基因富集在腺体发育、VEGF⁃A复合物等过程,KEGG通路富集显示主要富集在化学致癌作用受体激活、VEGF信号通路等通路上。药物活性成分共同靶点通路疾病网络分析淫羊藿核心活性成分为槲皮素、木犀草素和山奈酚;UALCAN分析交集基因的表达与Gleason分级有明显相关性,GEPIA数据库验证显示VEGFA、PGR、AKR1B1、GSTM1基因在前列腺癌组织中表达降低。结论VEGFA、PGR、AKR1B1、GSTM1基因是淫羊藿抗前列腺癌的主要靶点,淫羊藿治疗前列腺癌的核心活性成为槲皮素、木犀草素和山奈酚,其中可能是通过VEGF信号通路等发挥治疗前列腺癌的作用。 Objective Based on network pharmacology and WGCNA methods,to explore the potential targets of Epimedium in the treatment of prostate cancer,in order to provide a theoretical basis for the clinical treatment of prostate cancer.Methods The active components of Epimedium and their corresponding target genes were obtained by TCMSP,ETCM database and 2020 edition of Pharmacopoeia.R language was used to analyze the difference of data set GSE46602.WGCNA screened the key genes of prostate cancer and obtained the target genes of Epimedium⁃prostate cancer intersection.GO and KEGG pathway enrichment analysis were further performed.STRING and Cytoscape software were used to construct protein interaction network and drug active ingredient⁃target⁃pathway⁃disease network.UALCAN website and GEPIA database were used to verify the correlation between key genes and Gleason grade.Results There were 31 effective active components of Epimedium,228 corresponding target genes,and 9 potential targets of Epimedium against prostate cancer.GO analysis showed that disease intersection genes were enriched in gland development,VEGF⁃A complex and other processes,and KEGG 112 Chinese Journal of Andrology Vol.38 No.22024 pathway enrichment showed that they were mainly enriched in chemical carcinogenesis⁃receptor activation,VEGF signaling pathway and other pathways.Drug⁃active ingredient⁃common target⁃pathway⁃disease network analysis Epimedium core activity became quercetin,luteolin and kaempferol;UALCAN analysis showed that the expression of intersection genes was significantly correlated with Gleason grade.GEPIA database verification showed that the expression of VEGFA,PGR,AKR1B1 and GSTM1 genes was decreased in prostate cancer tissues.Conclusion VEGFA,PGR,AKR1B1 and GSTM1 genes are the main targets of Epimedium anti⁃prostate cancer.The core activity of Epimedium in the treatment of prostate cancer is quercetin,luteolin and kaempferol,which may play a role in the treatment of prostate cancer through VEGF signaling pathway.
作者 受梦媛 方柔柔 刘一笑 吴小玉 孙娜 Shou Mengyuan;Fang Rourou;Liu Yixiao;Wu Xiaoyu;Sun Na(School of Public Health,Shaanxi University of Traditional Chinese Medicine,Xianyang 712046,Shaanxi,China)
出处 《中国男科学杂志》 CAS CSCD 2024年第2期111-118,共8页 Chinese Journal of Andrology
基金 陕西省自然科学基础研究计划项目(2024JC⁃YBMS⁃744) 陕西中医药大学研究生创新项目(CXSJ202322) 咸阳市2021年科学技术社会发展项目(2021ZDYF⁃SF⁃0017)。
关键词 前列腺癌 网络药理学 WGCNA 淫羊藿 prostate cancer network pharmacology WGCNA Epimedium
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