基于网络药理学的中药鸦胆子治疗肺癌的分子机制研究

A network pharmacology approch to uncover the molecular mechanism of brucea javanica on lung cancer

目的运用网络药理学的方法构建中药鸦胆子活性成分-靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨中药鸦胆子治疗肺癌的分子机制。方法利用TCMSP数据库结合文献挖掘筛选鸦胆子主要活性成分,利用TCMSP、BATMAN-TCM、GeneCards和OMIM数据库结合文献挖掘筛选活性成分靶点。采用Cytoscape3.7.2软件构建活性成分-作用靶点网络,String数据库构建蛋白相互作用网络,DAVID6.8数据库进行GO和KEGG通路分析。结果共筛选出鸦胆子活性成分19个,作用于81个靶点,得到基因本体GO条目53个,肺癌相关通路105条。根据网络拓扑学分析结果,推测木犀草素、鸦胆子素D、β-谷甾醇、鸦胆亭、鸦胆子苦醇和鸦胆醇为鸦胆子治疗肺癌的主要活性成分,作用于mTOR、FGF2、BCL2、AR、CASP3、MMP1、MMP2、AKT1、ALB、EGFR和IL6等关键靶点。通过调节PI3K-Akt、apoptosis、smallcelllungcan-er、non-smallcelllungcancer和microRNAsincancer等信号通路发挥治疗肺癌的作用。结论本研究应用网络药理学方法部分证实和预测了鸦胆子治疗肺癌的分子机制,为鸦胆子的进一步实验研究和临床应用奠定了基础。

Objective To systematically explore the molecular mechanism of brucea javanica in the treatment of lung cancer by network pharmacology.Methods The main active components of brucea javanica were obtained from TCMSP and literatures.The TCMSP,BATMAN-TCM,GeneCards and OMIM databases were used to predict and screen targets of active components.Cytoscape 3.7.2 software was used to construct the active components-targets network.String database was used to construct the protein-protein interaction(PPI)network,and DAVID 6.8 database was used for GO functional annotation and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Results Totally 19 components,81 targets,53 GO entries and 105 lung cancer-related pathways were obtained.According to the results of network topology analysis,it was speculated that luteolin,bruceine D,beta-sitosterol,bruceantin,brusatol and bruceantinol were the main active components in brucea javanica,acting on the targets of mTOR,FGF2,BCL2,AR,CASP3,MMP1,MMP2,AKT1,ALB,EGFR and IL6,etc.The KEGG pathways of PI3 K-Akt,apoptosis,small cell lung cancer,nonsmall cell lung cancer,microRNAs in cancer and so on,were adjusted to play its effects against lung cancer.Conclusion This study partially verified and predicted the pharmacological and molecular mechanism of brucea javanica against lung cancer,and laid a foundation for further experimental research and clinical rational application of brucea javanica.