“半夏⁃天南星”药对治疗肺癌的网络药理学研究

Mechanism of"Pinelliae rhizoma-Arisaematis rhizoma"in treatment of lung cancer based on network pharmacology

目的:基于网络药理学探讨半夏⁃天南星药对治疗肺癌的作用机制。方法:采用TCMSP数据库收集半夏、天南星的活性成分和靶点,并通过cytoscape3.7.0构建“药物⁃活性成分⁃靶点”网络图,同时检索DisGeNet数据库获得肺癌相关靶点。使用BisoGenet分别构建“活性成分靶点PPI网络”及“肺癌靶点PPI网络”,获取交集网络并对靶点进行筛选。利用AutoDockTools对主要活性成分和核心靶点进行对接验证。运用DAVID数据库进行GO生物过程及KEGG通路富集分析。结果:从半夏⁃天南星中筛选获得15个活性成分,包括β⁃谷甾醇、黄芩素、豆甾醇、卡文定碱和松柏苷等,作用于ESR1和CDK2等95个关键靶点,这些靶点主要富集在PI3K⁃Akt、MAPK、HIF⁃1、FoxO、TGF⁃β、Hippo、TNF、Notch、VEGF、cAMP等多条肺癌相关通路。分子对接结果表明药对的活性成分可以对核心靶点(ESR1和CDK2)发挥调控作用。结论:半夏⁃天南星药对治疗肺癌的作用体现了中药多成分、多靶点、多通路的特点,其作用机制可能是通过调控细胞周期、调控血管生成、调控肿瘤干细胞等多个方面发挥治疗肺癌的作用。本研究为后续进一步研究提供思路和借鉴。

Objective:To explore the mechanism of"Pinelliae rhizoma Arisaematis rhizoma"in treatment of lung cancer based on network pharmacology.Methods:The active components and their targets of“Pinelliae rhizoma Arisaematis rhizoma”were screened out from TCMSP database.The cytoscape3.7.0 software was used to construct the drugactive componenttargets network.The DisGeNet database was searched to obtain lung cancer related targets.BisoGenet was used to construct"PPI net work of active component target"and"PPI network of lung cancer target",and the intersection of the two networks was taken and the target was screened.AutoDockTools software was used to dock the key active ingredients with the key targets.DAVID data base was used to perform GO biological process enrichment analysis and KEGG pathway enrichment analysis.Results:A total of 15 active components were collected,including betasitosterol,baicalein,stigmasterol,cavidine,coniferin,etc.These active components mainly acted on 95 key targets such as ESR1 and CDK2,which enriched in multiple lung cancer related signaling path ways,such as PI3KAkt,MAPK,HIF1,FoxO,TGFβ,Hippo,TNF,Notch,VEGF,cAMP,etc.The results of molecular dock ing showed that the active components could regulate the core targets(ESR1 and CDK2).Conclusion:The effect of“Pinelliae rhizoma Arisaematis rhizoma”in the treatment of lung cancer embodies the characteristics of multicomponent,multitarget and multipathway of traditional Chinese medicine.Its mechanism of action may be to play a role in the treatment of lung cancer by reg ulating cell cycle,angiogenesis,tumor stem cells,etc.This research can provide ideas and references for further research.