女贞子-黄芪治疗转移性去势抵抗性前列腺癌的网络药理学机制  

Mechanism of Ligustrum lucidum-Astragalus membranaceus in the Treatment of Metastatic Castration-Resistant Prostate Cancer Based on Network Pharmacology

作　　者：陈海群 华其荣 林军[2] 周青鸟[3] 陈嘉 覃菲 王璐 吴群英[2] CHEN Haiqun;HUA Qirong;LIN Jun;ZHOU Qingniao;CHEN Jia;QIN Fei;WANG Lu;WU Qunying(School of Pharmacy,Guilin Medical University,Guilin,Guangxi,541004,China;School of Intelligent Medicine and Biotechnology,Guilin Medical University,Guilin,Guangxi,541004,China;School of Basic Medical Sciences,Guangxi Medical University,Nanning,Guangxi,530021,China)

机构地区：[1]桂林医学院药学院,广西桂林541004 [2]桂林医学院智能医学与生物技术学院,广西桂林541004 [3]广西医科大学基础医学院,广西南宁530021

出　　处：《广西科学》2023年第5期1017-1024,共8页Guangxi Sciences

基　　金：国家自然科学基金项目(31100963);广西自然科学基金项目(2020JJB140154);2021年度广西壮族自治区教育厅项目(JGY2021134);桂林医学院博士科研启动基金项目和桂林医学院大学生创新创业项目(202010601161)资助。

摘　　要：本研究利用数据挖掘和网络药理学探讨女贞子(Ligustrum lucidum)-黄芪(Astragalus membranaceus)治疗转移性去势抵抗性前列腺癌(Metastatic Castration-Resistant Prostate Cancer,mCRPC)的作用机制。利用中药系统药理学(Traditional Chinese Medicine Systems Pharmacology,TCMSP)数据库与分析平台检索女贞子-黄芪的有效成分和作用靶点;利用R语言对芯片数据集GSE77930进行分析,筛选差异表达的基因;利用Cytoscape 3.8.0软件构建有效成分-靶点网络及蛋白互作网络;利用R语言对核心靶点进行GO富集分析和KEGG分析;采用Cytoscape 3.8.0软件构建女贞子-黄芪活性成分-靶点通路关系网络。结果表明女贞子-黄芪的关键活性成分共33个,包括槲皮素(Quercetin)、山奈酚(Kaempferol)、木犀草素(Luteolin)、异鼠李素(Isorhamnetin)、芒柄花黄素(Formononetin)等;核心作用靶点18个,其中AR、VCAM1、PCNA、NTRK1、TP53、EGFR和FBXO6等靶点可能是女贞子-黄芪治疗mCRPC的重要靶点。KEGG分析发现,女贞子-黄芪主要通过乙型肝炎(Hepatitis B)、前列腺癌(Prostate Cancer,PCa)、细胞周期(Cell cycle)、Vascular Endothelial Growth Factor(VEGF)信号通路(VEGF signaling pathway)和细胞衰老(Cellular senescence)等通路发挥抗mCRPC的作用。本研究结果可为mCRPC的临床治疗提供参考。In this study,data mining and network pharmacology were used to explore the mechanism of Ligustrum lucidum-Astragalus membranaceus in the treatment of metastatic Castration-Resistant Prostate Cancer(mCRPC).The effective components and targets of L.lucidum-A.membranaceus were retrieved by Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and analysis platform.The chip data set GSE77930 was analyzed by R language to screen differentially expressed genes.Cytoscape 3.8.0 software was used to construct the active ingredient-target network and protein interaction network.GO enrichment analysis and KEGG analysis of core targets were performed using R language.Cytoscape 3.8.0 software was used to construct the relationship network of L.lucidum-A.membranaceus active ingredient-target pathway.The results showed that there were 33 key active components in L.lucidum-A.membranaceus,including Quercetin,Kaempferol,Luteolin,Isorhamnetin,and Formononetin,etc.There were 18 core targets,among which AR,VCAM1,PCNA,NTRK1,TP53,EGFR and FBXO6 might be important targets for the treatment of mCRPC by L.lucidum-A.membranaceus.KEGG analysis showed that L.lucidum-A.membranaceus played an anti-mCRPC role mainly through Hepatitis B,Prostate cancer,cell cycle,VEGF signaling pathway and cellular senescence.The results of this study can provide a reference for the clinical treatment of mCRPC.

关 键 词：女贞子 黄芪 转移性去势抵抗性前列腺癌 网络药理学 作用机制 信号通路 

分 类 号：R285[医药卫生—中药学]