黄芪-党参药对治疗胃癌的网络药理学研究

目的运用网络药理学探讨黄芪-党参药对治疗胃癌的作用机制。方法通过DisGeNET数据库检索胃癌的相关靶点。使用中药系统药理学分析平台(TCMSP)检索黄芪、党参的潜在活性成分和作用靶点,借助PubChem数据库,预测黄芪-党参药对活性成分的所有潜在靶点,并将活性成分预测的靶点与疾病靶点取交集,获取黄芪-党参药对治疗胃癌的靶点集。使用Auto Dockt Vina对筛选所得的主要活性成分及主要相关靶点进行分子对接验证。通过DAVID进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。运用Cytoscape 3.7.1构建"药物-化合物-靶点-通路-疾病"网络及蛋白相互作用(PPI)网络,研究其作用机制。结果"药物-化合物-靶点-通路-疾病"网络包括52个活性化合物、62个作用靶点以及34条通路,关键化合物为3-β-Hydroxymethyllenetanshiquinone、黄芪皂苷Ⅰ、咖啡酸、异阿魏酸等,关键靶点涉及MAPK、PI3Ks、EGFR、NF-κB1等;PPI网络关键靶点主要为STAT3、PIK3CA、MAPK1、HRAS等。GO富集分析共涉及264个生物过程(BP),38个细胞组分(CC)以及57个分子功能(MF);KEGG通路富集分析筛选得到34条与胃癌相关的通路,主要为癌症通路、PI3K-Akt信号通路等。结论黄芪-党参药对可能是通过介导PI3K-Akt等信号通路调控肿瘤细胞的增殖、凋亡、迁移、失巢凋亡及血管生成等生物过程进而达到治疗胃癌的目的。

Network Pharmacology Study of Huangqi(Astragalus Membranaceus)-Dangshen(Codonopsis Pilosula)in Treatment of Gastric Cancer

Objective To explore the mechanism of Huangqi(Astragalus membranaceus)-Dangshen(Codonopsis pilosula)treating gastric cancer by using network pharmacology.Methods The relevant targets of gastric cancer were retrieved through the DisGeNET database.The Chinese Medicine System Pharmacology Analysis Platform(TCMSP)was used to search for the potential active components and targets of Huangqi(Astragalus membranaceus)-Dangshen(Codonopsis pilosula).The PubChem database was used to predict all potential targets for active components in Huangqi(Astragalus membranaceus)-Dangshen(Codonopsis pilosula).The intersection of the predicted targets and the disease targets was taken to obtain a target set for the treatment of gastric cancer by Huangqi(Astragalus membranaceus)and Dangshen(Codonopsis pilosula).Molecular docking verification of the screened components and targets was performed by using Auto Dockt Vina.Functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed by using DAVID.Cytoscape 3.7.1 was used to construct a"drugs-compounds-targets-pathways-diseases"network and protein-protein interaction(PPI)network to study its mechanism.Results The"drugs-compounds-targets-pathways-diseases"network contained 52 active compounds,62 targets and 34 pathways.The key compounds were 3-β-hydroxymethyllenetanshiquinone,saponinⅠ,caffeic acid and isoferulic acid,etc.The key targets involved MAPK,PI3 K,EGFR and NF-κB1,etc.The key targets of PPI network were STAT3,PIK3 CA,MAPK1 and HRAS.The GO enrichment analysis involved 264 biological processes(BP),38 cell components(CC)and 57 molecular functions(MF).KEGG pathway enrichment analysis found 34 channels associated with gastric cancer,mainly cancer pathway and PI3 K-Akt signal pathway.Conclusion Huangqi(Astragalus membranaceus)-Dangshen(Codonopsis pilosula)may be used to treat gastric cancer by transducing PI3 K-Akt and other signaling pathways to regulate the proliferation,apoptosis,migration,anoikis and angiogenesis of tumor cells.