摘要
目的 探讨五味消毒饮治疗乳腺癌的潜在活性成分及作用机制.方法 利用TCMSP数据库和DrugBank数据库检索五味消毒饮的相关化学成分及作用靶点,通过GeneCards数据库和OMIM数据库查找与乳腺癌相关的靶点,在VENNY 2.1 在线平台筛选交集基因,运用String 12.0 构建蛋白互做网络(PPI),使用DAVID数据库进行GO和KEGG富集分析,并以Autodock Vina验证靶点结合能力.结果 数据库检索得到五味消毒饮40个潜在有效成分,374个目标靶点基因,799 个乳腺癌相关靶点,分析得出 137 个潜在靶点基因,构建PPI网络图得出五味消毒饮治疗乳腺癌的9 个关键基因和 5 个关键化学成分.GO富集结果显示其生物学过程主要为参与激酶活性调节、RNA聚合酶Ⅱ转录因子活性调节、转录激活因子的结合等,KEGG通路富集结果显示 144 条相关通路主要涉及内分泌抵抗信号通路、白细胞介素-17(IL-17)信号通路、ErbB信号通路、催乳素信号通路、VEGF信号通路等.分子对接模拟结果表明关键活性成分与核心靶点蛋白均有较强的结合能力.结论 五味消毒饮治疗乳腺癌主要通过槲皮素、木犀草素、山奈酚、岩藻黄质和β-谷甾醇等活性成分影响了TP53、STAT3、AKT1、ESR1 等乳腺癌靶基因和 144 条相关信号通路.该方在乳腺癌治疗过程中具有多成分、多途径、多靶点、多机制的特点,为后续开发利用提供了新的思路.
Abstract
Objective To explore the potential active ingredients and mechanism of WuWeiXiaoDuYin in the treatment of breast cancer.Methods TCMSP database and DrugBank database were used to retrieve the related chemical components and targets of WuWeiXiaoDuYin,GeneCards database and OMIM database were used to find the targets related to breast cancer,the intersection genes were screened on the VENNY 2.1 online platform,String 12.0 was used to construct an egg white interaction network(PPI),DAVID database was used to carry out GO and KEGG enrichment analysis,and Autodock Vina was used to verify the target binding ability.Results 40 potential active ingredients,374 target genes and 799 breast cancer related targets of WuWeiXiaoDuYin were obtained through database retrieval and analysis,137 potential target genes were obtained through analysis,and 9 key genes and 5 key chemical components of WuWeiXiaoDuYin in the treatment of breast cancer were obtained by constructing PPI network map.The GO enrichment results showed that its biological processes mainly involve kinase activity regulation,RNA polymerase Ⅱ transcription factor activity regulation,and transcription activator binding.The KEGG pathway enrichment showed that 144 related pathways mainly involve endocrine resistance pathway,IL-17 pathway,ErbB pathway,prolactin pathway,VEGF pathway,etc.The molecular docking simulation results indicate that the key active ingredients have strong binding ability with core target proteins.Conclusion WuWeiXiaoDuYin mainly affects TP53,STAT3,AKT1,ESR1 and other breast cancer target genes and 144 related signal pathways in the treatment of breast cancer through active ingredients such as quercetin,luteolin,and kaempferol.This prescription has the characteristics of multi-component,multi-channel,multi target and multi mechanism in the treatment of breast cancer,which provides a new idea for subsequent development and utilization.
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