基于网络药理学探讨复康灵治疗三阴性乳腺癌的作用机制  

Exploring mechanism of Fukangling on triple negative breast cancer based on network pharmacology

作　　者：张玉柱 李甜 唐润薇 袁帅 余秋阳 张卫红[1] ZHANG Yuzhu;LI Tian;TANG Runwei;YUAN Shuai;YU Qiuyang;ZHANG Weihong(Baoshan Branch,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201999,China)

机构地区：[1]上海中医药大学附属曙光医院宝山分院,上海201999

出　　处：《上海中医药大学学报》2022年第S01期210-219,共10页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81904206);上海市卫健委卫生行业临床研究专项(202140239);上海市科委科研基金项目(21ZR1447800);上海市卫健委中医药传承和科技创新项目(ZYCC2019020);宝山区名中医传承工作室项目(BSMZYGZS-201909)

摘　　要：目的:运用网络药理学方法筛选中药复方复康灵的活性成分以及作用于三阴性乳腺癌干细胞的靶点和通路,探讨其分子机制。方法:通过TCMSP数据库、TCMID数据库和BATMAN-TCM数据库筛选出复康灵活性成分及其相关靶标;通过GeneCards数据库和GEO数据库收集疾病相关基因,并做交集筛选目标基因;运用String数据库构建蛋白相互作用(PPI)网络;采用DAVID数据库对复康灵关键作用靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析。结果:通过筛选得到复康灵有效成分108个和对应的靶基因446个,与三阴性乳腺癌干细胞的交集基因为49个;GO分析结果显示复康灵活性成分的基因功能主要表现在信号调控、细胞刺激反应、氧化应激反应、细胞凋亡、炎症反应以及对细胞因子刺激的反应等生物过程中,其抗三阴性乳腺癌的复发和转移的作用主要是通过调控细胞增殖、迁移等生物过程;KEGG分析结果显示其主要通过调控肿瘤坏死因子(TNF)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、核转录因子-κB(NF-κB)信号通路、肿瘤通路、表皮生长因子受体(EGFR)酪氨酸激酶抑制剂耐药等发挥治疗作用。结论:预测了复康灵对三阴性乳腺癌干细胞的作用靶点、物质基础和分子机制,以及复康灵对三阴性乳腺癌转移的分子机制。Objective:The network pharmacology was used to screen the active components of Fukangling and their targets and pathways on triple negative breast cancer stem cells,and explore the molecular mechanism.Methods:TCMSP database,TCMID database and BATMAN-TCM database were used for screening active components of Fukangling and related targets.Disease-related genes were collected through GeneCards database and GEO database,and target genes were obtained by intersection.The protein interaction(PPI)network was constructed using String database.The key targets of Fukangling were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)using DAVID database.Results:108 active ingredients of Fukangling and 446corresponding target genes were obtained,and there were 49 genes associated with triple negative breast cancer stem cells.GO analysis showed that the gene function of Fukangling active compounds mainly manifested in biological progresses such as signal regulation,cell stimulation response,oxidative stress response,apoptosis,inflammatory response,and response to cytokine stimulation.Its anti-recurrence and metastasis against triple negative breast cancer is mainly through biological processes like regulating cell proliferation and migration.KEGG analysis showed that it mainly exerts therapeutic effects by regulating tumor necrosis factor(TNF)signaling pathway,mitogenactivated protein kinase(MAPK)signaling pathway,nuclear transcription factor-κB(NF-κB)signaling pathway,tumor pathway,epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor resistance and so on.Conclusion:The targets,material basis and molecular mechanism of Fukangling on breast cancer stem cells,and its molecular mechanism were predicted.

关 键 词：复康灵 三阴性乳腺癌干细胞 网络药理学 通路 分子机制 

分 类 号：R285[医药卫生—中药学]