机构地区:[1]延安大学医学院,延安市肿瘤防治重点实验室,陕西延安716000
出 处:《延安大学学报(医学科学版)》2022年第4期21-28,共8页Journal of Yan'an University:Medical Science Edition
基 金:陕西省特支计划“区域人才”项目。
摘 要:目的基于网络药理学分析土茯苓治疗乳腺癌的作用机制。方法通过中药系统药理学数据库分析平台(the Traditional Chinese Medicine Database Analysis Platform,TCMSP)获取土茯苓的主要活性成分及其靶点。以TCMSP预测的活性成分为基础,通过Swiss、SEA、TCMSP和PharmMapper数据库预测、合并土茯苓主要活性成分的靶点;从OMIM、CTD、Genecards、PharmGKB和DisGeNET数据库获取乳腺癌主要作用靶点;通过取交集到土茯苓与乳腺癌的共同靶点;STRING数据库对共同靶点进行蛋白-蛋白相互作用(protein-protein interaction network,PPI)分析、Cytoscape 3.8.2软件构建PPI网络;采用Metascape平台对核心靶点进行GO富集分析与KEGG信号通路富集分析,并利用微生信在线绘图平台进行可视化处理。结果从土茯苓中筛选得到15种活性成分及614个作用靶点,与2195个乳腺癌相关靶点取交集,得到273个共同靶点;土茯苓治疗乳腺癌的有效活性成分有异黄杞苷、花旗松素、槲皮素、柚皮素、落新妇苷、谷甾醇、β-谷甾醇、豆甾醇和薯蓣皂苷元等;关键靶点为RAC-α丝氨酸/苏氨酸-蛋白激酶、肿瘤细胞抗原、表皮生长因子受体等;涉及生物学通路较多,主要功能有细胞代谢、细胞生长、细胞增殖、转移、凋亡和血管生成等,且多数通路与PI3K/AKT信号通路相关。结论土茯苓治疗乳腺癌具有多成分、多靶点、多通路的特点,通过分子网络的内在联系预测到土茯苓可能通过PI3K/AKT信号通路发挥治疗乳腺癌的作用,这为其实验研究和临床应用提供了一定的理论基础。Objective To explore the mechanism of Smilacis Glabrae Rhixoma in breast cancer therapy.Methods The main active compounds and their targets of Smilacis Glabrae Rhixoma were origin obtained from the Traditional Chinese Medicine Database Analysis Platform(TCMSP).The main active compounds targets of Smilacis Glabrae Rhixoma contained in both TCMSP,Swiss、SEA and PharmMapper were picked and used as the main function targets of Smilacis Glabrae Rhixoma.Breast cancer targets were obtained through OMIM,CTD,Genecards,PharmGKB and DisGeNET databases.Based on the above results,interactive targets between Smilacis Glabrae Rhixoma and breast cancer were obtained using Venn diagram.Protein-protein interaction(PPI)network of the interactive targets was STRING database analyzed,and Cytoscape 3.8.2 software constructed.GO enrichment and KEGG signaling pathway analysis of the interactive targets were performed using the Metascape platform.Results Fifteen active ingredients and 614 action targets were screened from Smilacis Glabrae Rhixoma,and 273common targets were obtained by intersection with 2195 breast cancer related targets.The effective active compounds of Smilacis Glabrae Rhixoma in the treatment of breast cancer were isoengelitin,taxifolin,quercetin,naringenin,astilbin,sitosterol,β-sitosterol,stigmasterol and diosgenin.The key targets of Smilacis Glabrae Rhixoma on breast cancer therapy were RAC-αSer/Ther protein kinase,tumor cell antigen,epidermal growth factor receptor.The biological pathway of Smilacis Glabrae Rhixoma in breast cancer treatment involved in cancer cells metabolism,growth,proliferation,metastasis,apoptosis and angiogenesis,many of them interact with PI3K/Akt.Conclusion Smilacis Glabrae Rhixoma works in breast cancer therapy through many compounds,targets and pathways.Besides,it functions in breast cancer therapy mainly by PI3K/AKT pathway.The result of this research provides some theoretical basis for the experimental research and clinical application of Smilacis Glabrae Rhixoma in breast cancer thera
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