基于网络药理学和分子对接技术探究槲皮素治疗非小细胞肺癌的作用机制  

Action Mechanism of Quercetin in Treating NSCLC Based on Network Pharmacology and Molecular Docking

作　　者：韩坤余 熊常州 夏雪 高朗 王怡丁 蔡政[3] 吴继萍[3] 牛华涛[4] HAN Kunyu;XIONG Changzhou;XIA Xue;GAO Lang;WANG Yiding;CAI Zheng;WU Jiping;NIU Huatao(The First Affiliated Hospital of Yunnan University of Chinese Medicine,Kunming 650021,China;Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Yunnan Provincial Hospital of Traditional Chinese Medicine,Kunming 650021,China;Yunnan Cancer Hospital,Kunming 650118,China)

机构地区：[1]云南中医药大学第一附属医院,云南昆明650021 [2]成都中医药大学,四川成都610075 [3]云南省中医医院,云南昆明650021 [4]云南省肿瘤医院,云南昆明650118

出　　处：《中医药信息》2022年第6期41-47,共7页Information on Traditional Chinese Medicine

基　　金：云南省应用基础研究(昆医联合专项)项目(202001AY070001-247);CSCO-齐鲁肿瘤研究基金项目(Y-Q201802-048)。

摘　　要：目的:基于网络药理学和分子对接技术探究槲皮素治疗非小细胞肺癌(NSCLC)的作用机制。方法:从GEO数据库选取基因芯片(GSE19188)获得NSCLC相关靶点,并与槲皮素作用靶点映射,使用Cytoscape软件构建“槲皮素-靶点-NSCLC”网络。采用STRING数据库和Cytoscape构建靶标蛋白互作网络并进行拓扑分析,运用ClusterProfiler包进行GO和KEGG富集分析。最后利用AutoDock Vina进行分子对接验证。结果:本研究共预测得到33个槲皮素治疗NSCLC的潜在靶点,利用Cytoscape中MCODE插件构建“槲皮素-靶点-NSCLC”网络和关键模块,筛选得到15个关键基因和3个功能模块。GO和KEGG分析表明核心靶点参与凋亡过程的负调控、蛋白水解等15条生物学过程,作用于癌症信号通路、TNF、PPAR、IL-17和细胞色素P450等15个信号通路。分子对接显示槲皮素与PPI中的核心靶点具有良好对接活性。生存分析显示核心基因与NSCLC患者的五年总生存率具有显著相关性。结论:本研究初步揭示了槲皮素抗NSCLC多靶点、多通路的作用机制,为槲皮素抗NSCLC研究及临床应用提供了理论依据。Objective:To explore the action mechanism of quercetin in the treatment of non-small cell lung cancer(NSCLC)based on network pharmacology and molecular docking.Methods:Gene chip(GSE19188)was selected from GEO database to obtain NSCLC related targets,which were mapped with quercetin action targets,and Cytoscape software was used to construct’quercetin-target-NSCLC’network.The target protein interaction network was constructed by string database and Cytoscape,and the topology was analyzed.The ClusterProfiler package was used for GO and KEGG enrichment analysis.Finally,AutoDock Vina was used for molecular docking verification.Results:In this study,33 potential targets for quercetin treating NSCLC were predicted.The’quercetin-target-NSCLC’network and key modules were constructed by using the MCODE plug-in of Cytoscape,and 15 key genes and 3 functional modules were screened.GO and KEGG analysis showed that the core target participated in 15 biological processes,such as negative regulation of apoptosis and protein hydrolysis,and acted on 15 signal pathways,such as signal pathways of cancer,TNF,PPAR,IL-17 and cytochrome P450.Molecular docking showed that quercetin had good docking activity with the core target in PPI.Surrival analysis showed that the core gene was significantly correlated with the five-year surrival rate of NSCLC patients.Conclusion:This study preliminarily revealed the multitarget and multi-pathway mechanism of quercetin against NSCLC,which provided a theoretical basis for the research and clinical application of quercetin against NSCLC.

关 键 词：网络药理学 分子对接 槲皮素 非小细胞肺癌 作用机制 

分 类 号：R285[医药卫生—中药学]