基于网络药理学及分子对接的通关藤治疗非小细胞肺癌的现代机制

Modern Mechanism of Marsdenia Tenacissima in the Treatment of Non-Small Cell Lung Cancer Based on Network Pharmacology and Molecular Docking

目的:预测通关藤(marsdenia tenacissima,MT)治疗非小细胞肺癌(non-small-cell lung cancer,NSCLC)的有效成分及分子作用机制。方法:通过国内外文献报道,获取MT有效成分,并利用Swiss Target Prediction数据库寻找MT潜在靶点,通过TTD、Drugbank数据库获取NSCLC疾病靶点。利用可视化分析软件Cytoscape构建"MT-NSCLC-治疗靶点"网络,获得MT与NSCLC的共有靶点,根据网络拓扑性质,研究MT的主要活性成分。从STRING数据库获取蛋白互作(PPI)信息,并利用Cytoscape软件将PPI网络进行可视化处理,以筛选关键靶点。通过ClusterONE插件对关键靶点进行模块分析。利用分子对接筛选与关键靶点作用的主要活性成分。最后将共有靶点利用ClueGO插件进行GO富集分析、Reactome分析,以及在Enrichr数据库进行KEGG通路分析。结果:筛选出MT有效化学成分17个,有37个靶点作用于NSCLC。分子对接结果提示了MT皂苷H和MT皂苷A可能是MT抗NSCLC的重要活性化合物,参与介导免疫系统中的细胞因子信号传导、癌症和PI3K/Akt信号通路等多种疾病代谢信号通路发挥治疗NSCLC的作用,其中免疫系统中的细胞因子信号传导最为主要。结论:MT治疗NSCLC的作用机制与改善炎症微环境,抑制肿瘤血管新生,调控基因表达等有关。

Objective Predict the effective components and molecular mechanism of marsdenia tenacissima in the treatment of non-small-cell lung cancer(NSCLC).Methods Through domestic and foreign literature reports,obtain the effective components of the marsdenia tenacissima,use the Swiss Target Prediction database to predict its potential targets,and obtain the NSCLC disease targets through the TTD and Drugbank databases.The“Chinese materia medica-ingredients-target”network was constructed by Cytoscape software to obtain the common targets of marsdenia tenacissima and NSCLC.According to the network topology,the main active components of marsdenia tenacissima were predicted.With the help of STRING database and Cytoscape software,construct a protein interaction PPI network,screen key targets,and use ClusterONE plug-in to complete module analysis.Finally,use the ClueGO plug-in for common targets for GO enrichment analysis,Reactome analysis,and KEGG pathway analysis in the Enrichr database.Results Seventeen effective chemical constituents of marsdenia tenacissima were screened out,and there were 37 targets for NSCLC.The results of molecular docking suggested that tenacissoside H and tenacissoside A may be important active compounds of marsdenia tenacissima for NSCLC.It plays a role in the treatment of NSCLC by mediating cancer signaling pathways,cytokine signaling in the immune system,PI3K/Akt signaling pathways and other metabolic signaling pathways,among which cytokine signaling in the immune system is the most important.Conclusion The mechanism of marsdenia tenacissima in the treatment of NSCLC is related to improving the inflammatory microenvironment,inhibiting tumor angiogenesis,and regulating gene expression.