摘要
目的:利用网络药理学和分子对接的方法初步探究紫龙金片主要成分治疗非小细胞肺癌(NSCLC)的可能分子机制。方法:在中药系统药理学分析平台(TCMSP)中检索并提取紫龙金片主要成分(黄芪、当归、龙葵、丹参、半枝莲和郁金)的有效活性成分及相关作用靶点;通过GeneCards、DisGeNET以及OMIM数据库筛选出NSCLC相关基因作为疾病靶点。将有效成分靶点与疾病靶点取交集,运用STRING数据库构建疾病和药物共同靶点的蛋白⁃蛋白相互作用网络,使用Cytoscape 3.9.0软件CytoNCA插件筛选并明确紫龙金片主要成分治疗NSCLC的关键作用靶点。利用“clusterProfiler”R包对核心靶点基因进行GO和KEGG富集分析,并构建成分⁃靶点⁃通路网络图。最后对核心靶点及其相应成分进行分子对接验证。结果:通过筛选得到的药物有效活性成分175个,作用于860个靶点。药物靶点与疾病靶点的交集靶点共800个。通过Cytoscape 3.9.0软件蛋白互作网络的拓扑分析确定SRC、RELA、ESR1、HSP90AA1、EP300、STAT3、PIK3R1、AR、CREBBP、EGFR、EZH2、HRAS、MAPK1、MAPK3、JUN、HDAC1和PTPN11等可能是复方紫龙金片作用于NSCLC的关键靶点。对关键靶点的GO功能富集得到了1505个条目,包括生物过程1330个、分子功能117个、细胞组分58个。KEGG通路富集得到144条通路,大多涉及癌症相关的途径。分子对接结果表明活性成分与关键靶点之间具有较好的结合性。结论:本研究初步探索了紫龙金片主要成分治疗NSCLC的基本药理作用,其具有多成分、多靶点、多通路的特点。
Objective:To preliminarily explore the possible therapeutic mechanism of the main components of Zilongjin Tablet by using network pharmacology and molecular docking methods in the treatment of non⁃small cell lung cancer(NSCLC).Methods:The effective active components and relevant ac⁃tion targets of the main components of Zilongjin Tablet(Radix astragali,Angelica,Solanum,Sal⁃via miltiorrhiza,Scutellaria barbata,and Radix curcumae)were retrieved and extracted from Tradi⁃tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The rele⁃vant targets of NSCLC were screened by GeneCards,DisGeNET and OMIM databases.A protein⁃protein interaction(PPI)network between active component targets and disease targets was construct⁃ed by using the STRING database.Key role targets of the main components of Zilongjin Tablet to treat NSCLC were identified using the CytoNCA app in Cytoscape 3.9.0 software.The GO and KEGG enrichment analysis of the core targets were performed using the clusterProfiler R package.The“agentcomponent⁃target⁃pathway”network diagram was also constructed by Cytoscape 3.9.0 software.Finally,the relationship between the core targets and its corresponding components were verified by molecular docking.Results:A total of 175 drug active components acting on 860 targets were screyielded.There were 800 intersection targets between drug targets and disease targets.The topological analysis of PPI network in Cytoscape 3.9.0 software determined that SRC,RELA,ESR1,HSP90AA1,EP300,STAT3,PIK3R1,AR,CREBBP,EGFR,EZH2,HRAS,MAPK1,MAPK3,JUN,HDAC1,and PTPN11 might be key targets of the main components of Zilongjin Tablet acting on NSCLC.The GO functional enrichment analysis resulted in 1505 entries,including 1330 biological processes,117 molecular functions,and 58 cell components.The KEGG pathway enrichment analysis yielded 144 pathways,mostly involving cancer⁃associated pathways.The results from molecular docking indicated good binding between the active components and the key tar
作者
宋从宽
李东航
卢子龙
潘世泽
李宁
耿庆
SONG Congkuan;LI Donghang;LU Zilong;PAN Shize;LI Ning;GENG Qing(Dept.of Thoracic Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)
出处
《武汉大学学报（医学版）》
CAS
2023年第9期1078-1085,共8页
Medical Journal of Wuhan University
基金
国家自然科学基金资助项目(编号:81770095,81700093,8210082163)
中央高校基本科研专项基金(编号:2042021k0081)
湖北省自然科学基金创新群体(编号:2020CFAO27)。
关键词
紫龙金片
非小细胞肺癌
网络药理学
分子对接
作用机制
Zilongjin Tablet
Non⁃Small Cell Lung Cancer
Network Pharmacology
Molecu⁃lar Docking
Mechanism
