基于网络药理学联合GEO数据库及分子对接技术探讨化瘀丸治疗乳腺癌的作用机制  

Discussion on the Mechanism and of Huayu Pills in the Treatment of Breast Cancer Based on Network Pharmacology Combined with GEO Database and Molecular Docking Technology

作　　者：刘敏[1] 李羿南 张青[1] LIU Min;LI Yi-nan;ZHANG Qing(Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]首都医科大学附属北京中医医院,北京100010 [2]北京中医药大学,北京100029

出　　处：《中国中医药图书情报杂志》2022年第5期1-8,共8页Chinese Journal of Library and Information Science for Traditional Chinese Medicine

基　　金：恩施州科技计划研究与开发项目(JCY2019000040)。

摘　　要：目的 通过网络药理学联合GEO数据库差异基因分析及分子对接技术研究化瘀丸治疗乳腺癌的有效成分及作用机制。方法 利用TCMSP数据库检索化瘀丸中12味中药信息,获得化瘀丸的活性成分和分子靶点。通过GEO数据库检索“breastcancer”筛选后获得GSE139038数据,通过R软件分析得出差异基因。通过DrugBank、OMIM、TTD和CTD数据库筛选出乳腺癌的相关靶点,利用UniProt数据库对靶点进行基因注释,通过Cytoscape3.2.1软件构建化瘀丸与乳腺癌的成分-靶点网络图,使用插件BisoGenet和CytoNCA绘制核心靶点拓扑网络,并进行药物与疾病交集靶点的GO功能与KEGG通路富集分析,最后将网络中度值较高的成分与核心靶点进行分子对接。结果 从GEO数据库下载分析得到乳腺癌上调和下调最明显的差异基因40个。获得化瘀丸主要活性成分7个,包括山柰酚(kaempferol)、谷甾醇(sitosterol)、异鼠李素(isorhamnetin)、常春藤皂苷元(hederagenin)、槲皮素(quercetin)、β-谷甾醇(beta-sitosterol)和豆甾醇(stigmasterol)等,作用于JUN、FOS、MYC、E2F1、E2F2等32个基因靶点。GO功能与KEGG通路富集分析表明,化瘀丸治疗乳腺癌主要通过调节氧化应激、激活转录因子结合、趋化因子受体结合等生物反应,作用于病毒感染通路、细胞衰老信号通路、IL-17信号通路、肝癌通路等发挥治疗作用。结论 化瘀丸治疗乳腺癌的活性成分为槲皮素等,主要涉及病毒感染、IL-17及其他与癌症相关的通路。Objective To study the effective components and action mechanism of Huayu Pills in the treatment of breast cancer through the combination of GEO database differential gene analysis and molecular docking technology.Methods The TCMSP database was used to retrieve the information of 12 types of Chinese materia medica in Huayu Pills,and the active components and molecular targets of Huayu Pills were obtained.GSE139038 chip data were obtained from the GEO database through searching breast cancer,and the difference genes were analyzed through R software.Targets for the treatment of breast cancer were screened through DrugBank,OMIM,TTD and CTD databases.Gene annotation was performed on the target using the UniProt database.The composition-target network map of Huayu Pills and breast cancer was constructed by Cytoscape 3.2.1 software,and the core target topological network was plotted using plug-ins BisoGenet and CytoNCA.GO enrichment analysis and KEGG enrichment analysis were performed for drugs and disease genes.Finally,the components with high degree of the network were under molecular docking with the core target.Results From the GEO database,40 genes with the most significant difference of up-regulated and down-regulated breast cancer were obtained.7 effective active components of Huayu Pills were obtained,including kaempferol,sitosterol,isorhamnetin,hederagenin,quercetin,beta-sitosterol,stigmasterol,which acted on 32 gene targets including JUN,FOS,MYC,E2F1,E2F2,etc.GO function and KEGG pathway enrichment analysis showed that oxidative stress,activation of the transcription factor,chemokinine receptor binding and other aspects were mainly involved in the treatment of breast cancer by Huayu Pills.The pathways involved in virus infection,cellular senescence signaling pathway,IL-17 signaling pathway,and pathways in hepatocellular carcinoma.Conclusion The important active components of Huayu Pills in the treatment of breast cancer are quercetin,etc.,and virus infection,IL-17 and other signaling pathways of cancers are i

关 键 词：化瘀丸 乳腺癌 网络药理学 生物信息学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学] R273.79[医药卫生—中医学]