基于网络药理学探讨黄连和黄芪治疗鼻咽癌的作用机制

Mechanism of Coptis and Astragalus in treatment of nasopharyngeal carcinoma based on network pharmacology

目的通过网络药理学探讨黄连和黄芪治疗鼻咽癌的作用机制。方法采用中药系统药理学分析平台(TCMSP)获取黄连和黄芪的活性成分和作用靶点。通过Gene Cards数据库获取鼻咽癌相关靶点,应用R语言软件及Perl语言程序筛选出与黄连和黄芪的共同靶点。使用STRING数据库进行蛋白-蛋白相互作用(PPI)网络分析。应用Cytoscape 3.6.0软件构建成黄连和黄芪活性成分-鼻咽癌-靶点交集网络。通过R语言软件对共同靶点进行基因本体(GO)和基因功能(KEGG)富集分析。采用MTT法对活性成分抗增殖效应进行体外验证。结果共获得黄连和黄芪中19个活性成分,183个候选靶点,鼻咽癌相关靶点768个,两者匹配映射得到共同靶点95个,出现频次较高的有丝氨酸/苏氨酸激酶1(AKT1)、原癌基因(JUN)、丝裂原活化蛋白激酶(MAPK)1、RELA、白细胞介素(IL)-6等,主要涉及受体配体活性、细胞因子活性、蛋白激酶调节活性、DNA结合转录激活活性等生物过程,并主要富集在磷脂酰肌醇激酶(PI3K)/AKT信号通路、MAPK信号通路、IL-17信号通路、肿瘤坏死因子(TNF)信号通路等调控通路。MTT实验表明小檗碱和芒柄花黄素均能抑制人鼻咽癌CNE细胞增殖。结论黄连和黄芪中的槲皮黄素、山柰酚、芒柄花黄素、小檗碱等多成分可能通过PI3K-AKT、MAPK等多个信号通路作用于鼻咽癌。

AIM To explore the mechanism of Coptis and Astragalus in the treatment of nasopharyngeal carcinoma by network pharmacology.METHODS The active ingredients and targets of Coptis and Astragalus were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The disease targets of nasopharyngeal carcinoma were obtained from the GeneCards database.The common targets of Coptis and Astragalus were screened out by R language software and Perl language program.The protein-protein interaction(PPI)network was analyzed by STRING database,and the intersection network of active ingredients,nasopharyngeal carcinoma,and the targets was constructed by Cytoscape 3.6.0 software.The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis of common targets were analyzed by R language software.The anti-proliferative effect of active ingredients was verified in vitro by MTT method.RESULTS Through screening,19 active components,183 candidate targets from Coptis and Astragalus,and 768 therapeutic targets for nasopharyngeal cancer were obtained.Ninety-five common targets of Coptis and Astragalus were obtained through screening and intersection.The serine/threonine kinase(AKT)1,proto-oncogene(JUN),mitogen-activated protein kinase(MAPK)-1,RELA and interleukin(IL)-6 were found frequently.These targets were mainly involved in biological processes such as receptor-ligand activity,cytokine activity,protein kinase regulatory activity,DNA binding transcriptional activation activity,etc.They were mainly concentrated in phosphatidylinositol kinase(PI3K)/AKT,MAPK,IL-17,tumor necrosis factor(TNF),and other signal pathways.MTT assay showed that berberine and anthocyanin could inhibit the proliferation of human nasopharyngeal carcinoma CNE cells.CONCLUSION The components in Coptis and Astragalus such as quercetin,kaempferol,formononetin,berberine,etc.may act onnasopharyngeal carcinoma through PI3K-AKT,MAPK and other signal pathways.