基于网络药理学探讨蛇床子-补骨脂治疗乳腺癌骨转移的作用机制  

Exploration on the mechanism of Cnidii fructus-Psoralea fructus in treatment of bone metastasis of breast cancer based on network pharmacology

作　　者：柯昌虎[1] 严慧[2] 陈琴华 黄慧敏[3] 昝继斌 何晓东 KE Chang-hu;YAN Hui;CHEN Qin-hua(Department of Pharmacy,Sinopharm Dongfeng General Hospital,Hubei University of Medicine,Shiyan 442008,China)

机构地区：[1]湖北医药学院附属国药东风总医院药学部,十堰442008 [2]湖北医药学院附属国药东风总医院妇科,十堰442008 [3]湖北医药学院附属国药东风总医院实验中心,十堰442008 [4]深圳市宝安纯中医治疗医院药学部,广东518101

出　　处：《中国临床新医学》2023年第5期479-485,共7页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

基　　金：国家自然科学基金面上项目(编号:81872509);十堰市科技局科研项目(编号:22Y79);十堰市软科学研究计划项目(编号:2022R020);武当特色中药研究湖北省重点实验室(湖北医药学院)开放课题(编号:WDCM2022012)。

摘　　要：目的基于网络药理学探讨蛇床子-补骨脂治疗乳腺癌骨转移的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、中药分子机制的生物信息学分析工具(BATMAN-TCM)检索药物的化学成分,借助Swiss Target Prediction数据库获取药物成分对应的相关靶点;在GeneCards、在线人类孟德尔遗传(OMIM)数据库中检索乳腺癌骨转移的相关靶点;利用Venny 2.1在线软件获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物-成分-靶点-疾病网络;STRING数据库构建蛋白相互作用网络;借助DAVID数据库进行GO功能富集分析和KEGG通路富集分析。结果蛇床子-补骨脂中40个有效成分通过调控99个靶点和147条通路对乳腺癌骨转移产生作用。香叶木素、(E)-2,3-双(2-酮-7-甲氧基-甲氧羰基-8-基)丙烯醛、异补骨脂二氢黄酮、cniforin B、补骨脂甲素、O-乙酰异蛇床素、O-乙酰二氢欧山芹酯、补骨脂二氢黄酮甲醚、美花椒内酯、邻-异戊酰基二氢山芹醇、欧芹素、蛇床子素等成分可以通过表皮生长因子受体(EGFR)、RAC-α丝氨酸/苏氨酸蛋白激酶(Akt1)、类固醇受体辅助活化因子(SRC)等关键靶点介导癌症途径、内分泌抵抗、磷脂酰肌醇3激酶-丝氨酸/苏氨酸蛋白激酶(PI3K-Akt)、癌症中的蛋白聚糖、癌症中的微小RNA、癌症中的中心碳代谢、催乳素、细胞衰老、细胞凋亡、糖尿病并发症中的晚期糖基化终产物-晚期糖基化终产物受体(AGE-RAGE)、Ras、丝裂原活化蛋白激酶(MAPK)等信号通路来治疗乳腺癌骨转移。结论蛇床子-补骨脂可以通过多成分、多靶点、多途径参与乳腺癌骨转移的治疗,为其临床应用及治疗乳腺癌骨转移的机制深入研究提供了理论依据。Objective To explore the mechanism of Cnidii fructus-Psoralea fructus in treatment of bone metastasis of breast cancer based on network pharmacology.Methods The chemical components of drugs were retrieved by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),while the corresponding targets of the chemical components were obtained by the Swiss Target Prediction Database.The targets related to bone metastasis of breast cancer were retrieved in GeneCards,and Online Mendelian Inheritance in Man(OMIM)Database.Venny 2.1 online software was used to obtain the common targets of drugs-disease,and then the“drug-compound-target-disease”network diagram was constructed by using the software Cytoscape 3.8.2.The STRING database was used to draw the protein-protein interaction network,and the GO function enrichment and KEGG pathway enrichment analysis were carried out through the DAVID database.Results Forty active components of Cnidii fructus-Psoralea fructus could regulate 99 targets and 147 pathways to treat bone metastasis of breast cancer.Diosmetin,(E)-2,3-bis(2-keto-7-methoxy-chromen-8-yl)acrolein,isobavachin,cniforin B,cniforin A,O-isovalerylcolum bianetin,O-acetylcolumbianetin,bavachinin,xanthoxylin N,O-isovalyldihydrocarvinol,ostruthin and osthol could mediate pathways in cancer,endocrine resistance,phosphatidylinositol 3-kinase-serine/threonine kinase(PI3K-Akt),proteoglycans in cancer,microRNAs in cancer,central carbon metabolism in cancer,prolactin,cellular senescence,apoptosis,advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway in diabetic complications,Ras,mitogen-activated protein kinase(MAPK)and other signaling pathways through epidermal growth factor receptor(EGFR),RAC-alpha serine/threonine protein kinase(Akt1),steroid receptor coactivator(SRC)and other key target proteins to treat the bone metastasis of breast cance

关 键 词：蛇床子 补骨脂 乳腺癌骨转移 网络药理学 作用机制 

分 类 号：R285[医药卫生—中药学]