基于GEO芯片和网络药理学探讨康力欣胶囊治疗乳腺癌的作用机制

Research on the Mechanism of Kanglixin Capsule in the Treatment of Breast Cancer Based on GEO Chip and Network Pharmacology

目的:利用GEO芯片和网络药理学探讨康力欣胶囊治疗乳腺癌的分子机制。方法:通过TCMSP、HERB、Batman-TCM数据库检索药物的化学成分,借助Swiss Target Prediction数据库获取药物成分对应的相关靶点;在GEO数据库中检索乳腺癌的相关靶点;利用Venny 2.1.0在线软件获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物-成分-靶点-疾病网络;STRING数据库构建PPI网络;借助DAVID数据库进行GO功能富集和KEGG通路富集分析;运用AutoDock软件对关键的活性成分和靶点进行分子对接验证。结果:康力欣胶囊中59个有效成分通过调控106个靶点和43条通路对乳腺癌产生作用,法尼斯淝醇A、多胶阿魏素、宽叶阿魏酮、山奈酚、法尼斯淝醇B、泽兰黄醇素、槲皮素、宽叶阿魏醇、啤酒甾醇、阿魏种素等成分可以通过EGFR、JUN、PPARG、PTGS2、CCNA2、CHEK1、CDK1、CDK2、MMP9、TOP2A等关键靶点介导癌症的中枢碳代谢、细胞周期、代谢途径、癌症途径、AMPK、松弛素、FoxO、IL-17、Ras、HIF-1、MAPK、钙、胰岛素等信号通路来治疗乳腺癌。分子对接分析发现10个靶点蛋白与10个活性成分具有较好的结合能力。结论:康力欣胶囊可以通过多成分、多靶点、多途径参与乳腺癌的治疗,为其临床应用及治疗乳腺癌的机制深入研究提供了理论依据。

Objective To investigate the mechanism of Kanglixin capsule in breast cancer based on GEO chip and network pharmacology.Methods The chemical ingredients of drugs were collected by TCMSP,HERB and Batman-TCM database,while Swiss Target Prediction was used to predict the corresponding targets of ingredients.The targets of breast cancer were retrieved in GEO database.Venny 2.1.0 online software was used to obtain the common targets of drugs-disease,and then the"drug-compound-target-disease"net-work diagram was constructed by using the software Cytoscape 3.8.2.The STRING database was used to draw the PPI network,and the perform GO function and KEGG pathway enrichment analysis were carried out through DAVID database,and the AutoDock platform was applied in verifying the molecular docking of active components and protein targets.Results The 59 active components of Kanglixin capsule could regulate 106 targets and 43 pathways to treat breast cancer.Farnesiferol A,gummosin,conferone,kaempferol,farnesif-erol B,EUPATIN,quercetin,conferol,cerevisterol,assafoetidin and other active compounds,which could mediate central carbon metabolism in cancer,cell cycle,metabolic pathways,pathways in cancer,AMPK,relaxin,FoxO,IL-17 Ras,HIF-1,MAPK,calcium,insulin and other signaling pathways through EGFR,JUN,PPARG,PTGS2,CCNA2,CHEK1,CDK1,CDK2,MMP9,TOP2A and other key target proteins.Molecular docking analysis showed that 10 target proteins had good binding ability with 10 active components.Conclusion Kanglixin capsule can participate in the treatment of breast cancer through multiple components,targets and pathways,which provides a theoretical basis for the clinical application of Kanglixin capsule and the mechanism of its treatment of breast cancer.