崔学教治疗前列腺癌自拟方作用机制的网络药理学探讨

Mechanism of Cui Xuejiao’s Self- made Prescription in Treatment of Prostate Cancer Based onNetwork Pharmacology

目的通过网络药理学方法,对崔学教教授前列腺癌自拟方治疗前列腺癌的潜在机制进行预测分析。方法使用TCMSP、TCMID数据库检索并查阅文献获得自拟方15味药物的主要活性成分及作用靶点;利用GeneCards等数据库查询疾病靶点;利用Venn软件获取药物与疾病共同靶点;通过String平台与Cytoscape 3.7.2软件对共同基因进行蛋白互作网络分析;利用David、Metascape数据库对共同基因进行GO、KEGG等生物通路富集分析,使用GEPIA数据库验证关键基因表达量。结果自拟方15味药物共得到140个活性成分及278个靶点,前列腺癌疾病靶点11046个,二者共同靶点260个,根据度值分析,关键活性成分为quercetin、kaempferol、luteolin、ursolic acid,关键靶点为PTGS2、PTGS1、PRSS1、AR。蛋白互作网络分析显示核心靶点为CXCL8与APP。GO分析得到2665个条目,主要包括生物刺激、生物调节、细胞代谢等;KEGG富集分析得到202个条目,主要涉及癌症、细胞周期、细胞凋亡、血管生成等。根据-log10P确定Pathways in cancer为首要通路。结论崔学教教授自拟方通过多靶点、多通路的协同作用,抑制肿瘤细胞增殖,促进凋亡,抑制迁移及血管生成,从而达到其抑制前列腺癌的目的。

Objective To predict and analyze the potential mechanism of Professor Cui Xuejiao’s self-made prescription in the treatment for prostate cancer by network pharmacology.Methods The TCMSP,TCMID database and the literature searching were used to search for the main ingredients and the targets.GeneCards and other databases were used to query disease targets.Venn software was used to obtain the common targets of drugs and disease.The String database and Cytoscape software were used to construct the PPI network;and the David and Metascape database were used to perform GO function,KEGG pathway and other biological pathways enrichment analysis on common targets.The GEPIA database was used to verify expression levels of the hub gene.Results A total of 140 ingredients and 278 targets were obtained from 15 drugs,and 11046 disease targets for prostate cancer were identified,within which 260 were common targets for both.According to the degree scores,the key components were quercetin,kaempferol,luteolin,ursolic acid;and the core targets were PTGS2,PTGS1,PRSS1,AR.PPI network analysis revealed that CXCL8 and APP were the core targets.GO enrichment analysis gained 2665 entries,mainly include biological stimulation,biological regulation,cell metabolism;KEGG pathwayenrichment analysis identified 202 signal pathways,which mainly related to cancer,cell cycle,apoptosis,andangiogenesis. According to -log10P,pathways in cancer ranked the top one in the pathways. Conclusion ProfessorCui Xuejiao’s self-made prescription may have a multi-target and multi-pathway synergistic effect on the treatmentof prostate cancer. It can enhance the anti- tumor effects by inhibiting cell proliferation, promoting apoptosis,inhibiting migration,and inhibiting tumor angiogenesis,and so on.