基于网络药理学探讨槲皮素治疗肺癌的分子作用机制

Molecular Mechanism of Quercetin in the Treatment of Lung Cancer Based on Network Pharmacology

目的探讨槲皮素治疗肺癌(LC)的作用靶点及分子作用机制。方法利用TCMSP和SwissTargetPrediction数据库获得槲皮素相关靶点,利用GeneCards和OMIM数据库获得LC相关靶点,借助在线Venn网站得到槲皮素与LC交集靶点,通过STRING数据库构建PPI网络后导入Cytoscape 3.7.2软件得到槲皮素治疗LC的核心靶点,使用DAVID数据库进行基因本体(GO)、京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选出101个槲皮素治疗LC的作用靶点,其中槲皮素治疗LC的潜在核心靶点有23个,包括TP53、AKT1、EGFR、CASP3和VEGFA等;GO富集分析共得到880个条目,包括695个生物过程,64个细胞组成,121个分子功能;KEGG通路富集分析共得到156条通路,包括PI3K-AKT信号通路、MAPK信号通路以及microRNAs在癌症中的调控等。结论槲皮素可能通过TP53、AKT1、EGFR、CASP3和VEGFA等核心靶点介导PI3K-AKT、MAPK等信号通路及参与microRNAs调控发挥对LC的治疗作用。

Objective To explore the target and molecular mechanism of quercetin in the treatment of lung cancer(LC).Methods Quercetin and LC related targets were obtained by using TCMSP,SwissTargetPrediction,GeneCards and OMIM databases,and quercetin-LC intersection targets were obtained through the online Venn website,PPI network was constructed by STRING database,and then imported into Cytoscape 3.7.2 software to obtain the core targets of quercetin for LC,gene ontology(GO)and kyoto encyclopedia of genes and gnomes(KEGG)pathway enrichment analysis were performed by using the DAVID database.Results There were 101 potential targets of quercetin in the treatment of LC were screened,among which 23 potential core targets of quercetin for LC,including TP53,AKT1,EGFR,CASP3 and VEGFA,etc;GO enrichment analysis yielded a total of 880 entries,of which 695 were for biological processes,64 for cell components and 121 for molecular functions;KEGG pathway enrichment analysis showed 156 pathways,including PI3K-AKT signal pathway,MAPK signal pathway and regulation of microRNAs in cancer,etc.Conclusion Quercetin may play a therapeutic role in LC by mediating PI3K-AKT,MAPK and other signaling pathways and participating in the regulation of microRNAs through core targets such as TP53,AKT1,EGFR,CASP3 and VEGFA.