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

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。

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

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.