文献类型：期刊文献

中文题名：基于网络药理学探讨黄芪对NSCLC肿瘤微环境的调控机制

英文题名：Study on the Regulatory Mechanism of Astragalus membranaceus on Tumor Microenvironment of NSCLC Based on Network Pharmacology

作者：段海婧[1,2];曹如冰[1];臧凯宏[1,2];杜丽东[1,2];任远[1,2]

第一作者：段海婧

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃省中药药理与毒理学重点实验室,兰州730000

第一机构：甘肃中医药大学

年份：2020

卷号：36

期号：5

起止页码：120

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：甘肃省高等学校创新能力提升项目(编号:2019A-078)。

语种：中文

中文关键词：黄芪;非小细胞肺癌;肿瘤微环境;网络药理学;调控机制

外文关键词：Astragalus membranaceus;NSCLS;tumor microenvironment;network pharmacology;regulatory mechanism

摘要：目的:运用网络药理学方法分析黄芪主要活性成分对非小细胞肺癌(NSCLC)肿瘤微环境的调控机制,为进一步开发黄芪的药用价值提供参考。方法:通过TCMSP、ETCM、BATMAN-TCM数据库收集黄芪化学成分,筛选有效活性成分并预测其作用靶点;通过TTD、Drugbank、DisGeNET、pharmGKB数据库收集NSCLC相关靶点,通过GeneCards、NCBI-Gene数据库筛选肿瘤微环境相关靶点,采用Cytoscape软件构建黄芪活性成分-靶点-NSCLC-肿瘤微环境网络图,用STRING数据库分析共有靶点,构建PPI网络图,通过DAVID数据库对关键靶点蛋白进行GO功能富集分析和KEGG通路富集分析,预测黄芪调控NSCLC肿瘤微环境的潜在靶点。结果:检索出NSCLC疾病靶点2302个,从黄芪中共筛选出关键活性成分28个,其中3个活性化合物未找到相对应的靶点,其余25个化合物对应525个靶点,与NSCLC和肿瘤微环境均相关的靶点有124个,通过蛋白互作结果可知AKT1、ALB、CASP3、IL-6、ESR1、EGFR、JUN、CCND1这8个靶标与黄芪调节NSCLC肿瘤微环境相关性最大,这8个靶标即为核心靶点。黄芪调节NSCLC肿瘤微环境可能与TNF、HIF-1、MicroRNAs、T细胞受体,ErbB、Fox0、甲状腺激素、NOD-样受体、鞘脂类、p53、NF-κB、MAPK、VEGF信号通路有关。调控凋亡、RNA聚合酶II启动子转录、DNA转录、药物反应、细胞对缺氧的反应等多个生物过程,从而发挥调节NSCLC肿瘤微环境的作用。结论:黄芪调节NSCLC肿瘤微环境的作用机制可能与其多成分作用于多靶点,影响与NSCLC肿瘤微环境相关的多个信号通路,调节复杂的生物过程有关。
Objective:To study the potential mechanism of main acive components of Astragalus membranaceus on regulating the tumor microenvironment of non-small cell lung cancer(NSCLC)based on network pharmacology,in order to provide the reference for its further medininal development.Methods:The TCMSP,ETCM and BATMAN-TCM database were used to collect the chemical components and action targets of Astragalus membranaceus.The TTD,Drugbank,DisGeNET,pharmGKB database were used to collect the NSCLC-related targets,then Gene-Cards and NCBI-Gene databases were used to collect the targets related to the tumor microenvironment,the Cytoscape software was used to construct the active components,target and disease correlation network of Astragalus membranaceus.STRING database was used to to build PPI network,GO and KEGG enrichment were conducted by using DAVID database,in order to explore the potential targets of Astragalus membranaceus in regulating NSCLC tumor microenvironment.Results:2302 NSCLC disease targets were screened.28 active compounds were screened out from Astragalus membranaceus,while 3 active components of them had no related targets.The other 25 active components acted 525 targets,among which,124 were related to both tumor microenvironment and NSCLC.Protein interaction results showed that 8 targets including AKT1,ALB,CASP3,IL6,ESR1,EGFR,JUN,CCND1 were core targets,and they had significant relationship with Astragalus membranaceus regulating NSCLS.Astragalus membranaceus affected many signal pathways related to NSCLS tumor microenvironment,such as TNF,HIF-1,MicroRNAs,T-cell receptor,ErbB,FoxO,Thyroid hormone,NOD-like receptor,p53,NF-κB,MAPK、VEGF.It also regulated the biological processes such as the apoptotic process,the transcription from RNA polymerase II promoter,DNA transcription,the drug reaction,cellular response to hypoxia.Conclusion:The mechanism of Astragalus membranaceus in regulating tumor microenvironment of NSCLS may be related to its multi-components acting multiple targets,regulating complex biological processes and affecting multiple signal pathways related to NSCLS tumor microenvironment.