基于网络药理学探讨桔梗-苦杏仁与肺癌相关分子机制

目的:基于网络药理学方法筛选桔梗-苦杏仁药对中的活性成分,预测治疗癌症的作用靶点及信号通路,构建多成分-多靶点-多通路的相互作用网络,进一步探究其治疗肺癌的可能作用机制。方法:通过中药系统药理数据库和分析平台(TCMSP)以及文献查阅,检索并收集桔梗-苦杏仁的活性成分及其对应的靶标。利用UniProt数据库和Genecards数据库获得桔梗-苦杏仁治疗肺癌的潜在靶标基因。用Cytoscape 3.6.0软件构建"成分-靶标"网络。结合String数据库及Cytoscape软件中的Generate style from statistics工具,构建蛋白质相互作用网络。通过Systems Dock Web Site网络服务器与桔梗-苦杏仁的活性成分进行分子对接。利用功能注释生物信息学分析平台(DAVID)数据库,对桔梗-苦杏仁的作用靶标进行京都基因与基因组百科全书(KEGG)通路富集分析和基因本体(GO)分类富集分析。结果:共筛选得到桔梗-苦杏仁的14个活性成分,包括acacetin,cis-dihydroquercetin,spinasterol,licochalcone B,luteolin等,和103个作用靶标,包括诱导型一氧化氮合酶蛋白(NOS2),环加氧酶1蛋白(PTGS1),雄激素受体(AR),环加氧酶2蛋白(PTGS2),二肽基肽酶4(DPP4)等,主要涉及prostate cancer,small cell lung cancer,hepatitis B,T cell receptor signaling pathway等信号通路。结论:该研究基于网络药理学的方法预测了桔梗-苦杏仁治疗肺癌的可能的作用机制,为后续的深入研究提供了方向。

Molecular Mechanism of Platycodonis Radix- Armeniacae Semen Amarum in Treating Lung Carcinoma Based on Network Pharmacology

Objective To screen out the active components of Platycodonis Radix-Armeniacae Semen Amarum, predict the targets and signaling pathways, construct the "multi-components, multi-targets and multi-pathways" interaction network and further investigate their molecular mechanism for the treatment of lung carcinoma based on network pharmacology.Method Active components and corresponding targets of Platycodonis Radix-Armeniacae Semen Amarum were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature consultation. Therapeutic targeted genes of Platycodonis Radix-Armeniacae Semen Amarum in the treatment of lung carcinoma were obtained from UniProt database and Genecards database. The "components-targets" network was constructed by using Cytoscape 3.6.0 software, and the protein-protein interactions network was constructed by String database and "Generate Style From Statistics" tool in Cytoscape software. Its molecular docking with active components of Platycodonis Radix-Armeniacae Semen Amarum was carried out by using Systems Dock Web Site network server. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis on the therapeutic targets of Platycodonis Radix-Armeniacae Semen Amarum were performed with the Database for Annotation, Visualization Andintegrated Discovery (DAVID).Result Fourteen active components of Platycodonis Radix-Armeniacae Semen Amarum were screened out, including acacetin, cis-dihydroquercetin, spinasterol, licochalcone B, and luteolin, et al. One hundred and three therapeutic targets were screened out, including nitric oxide synthase 2 (NOS2), prostaglandin endoperoxide synthase 1 (PTGS1), androgen receptor (AR), prostaglandin endoperoxide synthase 2 (PTGS2), and dipeptidyl peptidase 4 (DPP4), et al. Identified signaling pathways mainly involved prostate cancer signaling pathway, small cell lung cancer signaling pathway, hepatitis B signaling pathway and T cell receptor signaling pathway.Conclusion The possible molecular mechanism of Platycodonis Radix-Armeniacae Semen Amarum for the treatment of lung carcinoma was explored in this study based on network pharmacology, providing the direction for subsequent research.