基于网络药理学和分子对接技术探讨蟾酥治疗肺癌的作用机制

The Mechanism of Toad Cake in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking Technology

目的:采用网络药理学及分子对接技术探索蟾酥治疗肺癌的分子作用机制。方法:通过中药与化学成分数据库、BATMAN、SwissADME、SwissTargetPrediction数据库获取并筛选蟾酥的活性成分及作用靶点;通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、药物靶标数据库(therapeutic targetdatabase,TTD)获取肺癌主要靶点,利用STRING平台构建共同靶点蛋白-蛋白互作网络(protein-protein interactions,PPI);运用Cytoscape 3.7.1软件构建蟾酥活性成分-肺癌-靶点交集网络;通过R语言软件对共同靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;通过AutoDock Tools 1.5.6、AutoDock vina 1.1.2进行分子对接验证。结果:共筛选出蟾酥有效活性成分19个,蟾酥作用于肺癌的靶点94个,PPI网络显示表皮生长因子受体、丝裂原活化蛋白激酶3、丝裂原活化蛋白激酶1、白细胞介素6、类固醇受体辅激活因子等为核心靶点,主要涉及肽基-酪氨酸磷酸化及修饰、丝氨酸磷酸化及修饰等生物过程;蟾酥作用于肺癌的生物学通路主要富集在PI3K/Akt、癌症蛋白聚糖、癌症MicroRNAs等信号通路;分子对接结果证明蟾酥大部分有效活性成分与核心蛋白靶点有较好的结合活性。结论:蟾酥可通过多成分、多靶点、多通路治疗肺癌。

Objective:To explore the molecular mechanism of toad cake(bufonis venenum)in the treatment of lung cancer based on network pharmacology and molecular docking technology.Methods:We obtained and screened the active ingredients and targets of toad cake through the database of traditional Chinese medicine and chemical composition,BATMAN database,SwissADME,SwissTargetPrediction,and yielded the main targets of lung cancer through the human gene database(GeneCards),online mendelian inheritance in man(OMIM),and therapeutic targetdatabase(TTD),we constructed a common target protein-protein interactions(PPI)using String platform,and built the intersection network of active ingredients-lung cancer-targets of toad cake using Cytoscape 3.7.1 software,as well as carried out GO and KEGG pathway enrichment analysis of the shared targets using R language software,consequently,to perform molecular docking validation by AutoDock Tools 1.5.6 and AutoDock vina 1.1.2.Results:A total of 19 effective active ingredients of toad cake were screened,and 94 targets of toad cake in lung cancer were identified.The PPI network showed that EGFR,MAPK3,MAPK1,IL-6 and SRC were the core targets,mainly involved in the biological processes of peptidyl-tyrosine phosphorylation and modification,serine phosphorylation and modification,etc.The biological pathways of toad cake in lung cancer are mainly enriched in PI3K-Akt,cancer proteoglycans,and cancer MicroRNAs;the molecular docking results proved that most of the effective active ingredients of toad cake have better binding with the core protein targets.Conclusion:Toad cake is a multi-component,multi-target and multi-pathway drug for the treatment of lung cancer.