基于网络药理学探讨抗癌精方治疗胃癌的作用机制

Mechanism of Anti-cancer Essence Formula in the treatment of gastric cancer based on network pharmacology

目的:基于网络药理学探讨抗癌精方治疗胃癌药效物质基础及作用机制,为临床中药治疗胃癌提供生物信息学依据。方法:在中药系统药理数据库和分析平台(TCMSP)检索抗癌精方药物有效成分,结合UniProt数据库得到有效成分药物靶点,利用GeneCards、OMIM、TTD等数据库获得胃癌相关疾病靶点,使用Cytoscape 3.9.1软件构建“疾病-成分-靶点”网络,String数据库及Cytoscape软件构建PPI网络。通过UALCAN数据库分析核心基因的转录水平,Kaplan-Meier plotter数据库分析核心基因表达与患者生存之间的关系。通过DAVID数据库进行GO功能和KEGG通路富集分析。结果:抗癌精方活性成分236个,PPI网络筛选出16个关键靶点;MAPK3、MAPK1、RELA、AKT1、TP53、FOS、MAPK14、RXRA、MAPK8、EGFR在胃癌组织中异常表达(P<0.05),且均与胃癌患者预后呈相关性(P<0.05);GO功能分析主要富集于细胞分裂、细胞增殖凋亡等调控,KEGG通路富集分析主要富集于癌症通路、MAPK信号通路、Relaxin信号通路、TNF信号通路、T细胞受体信号通路、Prolactin信号通路、PI3K-Akt信号通路等。结论:抗癌精方具有多成分、多靶点、多途径的协同作用特点,主要通过槲皮素、山奈酚、β-谷甾醇、消旋卡文定碱等活性成分,作用于MAPK3、MAPK1、RELA、AKT1、TP53、FOS、MAPK14、RXRA、MAPK8、EGFR靶点,调控MAPK、Relaxin、TNF、T细胞受体、Prolactin、PI3K-Akt信号通路等发挥作用。

Objective:To investigate the pharmacological basis and mechanism of Anti-cancer Essence Formula in the treatment of gastric cancer based on network pharmacology,and to provide bioinformatics basis for the clinical treatment of gastric cancer with traditional Chinese medicine.Methods:The active ingredients of Anti-cancer Essence Formula were searched in TCMSP database,and the targets of the active ingredients were further obtained using UniProt database.The targets of gastric cancer were obtained using GeneCards,OMIM and TTD databases.Cytoscape 3.9.1 software was used to build the“Disease-Component-Target”network.String database and Cytoscape 3.9.1 software were used to construct the PPI network.The transcript levels of the core genes were analyzed by UALCAN database,and the relationship between core gene expression and patient survival was analyzed by Kaplan-Meier plotter.GO function and KEGG pathway enrichment analyses were performed by DAVID database.Results:There were 236 active ingredients of Anti-Cancer Essence Formula,and 16 key targets were screened by PPI network.MAPK3,MAPK1,RELA,AKT1,TP53,FOS,MAPK14,RXRA,MAPK8 and EGFR were abnormally expressed in gastric cancer tissues(P<0.05),and all of them showed correlation with the prognosis of gastric cancer patients(P<0.05).GO analysis was mainly enriched in cell division,cell proliferation and apoptosis,and KEGG analysis was mainly enriched in cancer pathway,MAPK signaling pathway,Relaxin signaling pathway,TNF signaling pathway,T-cell receptor signaling pathway,Prolactin signaling pathway,and PI3K-Akt signaling pathway.Conclusion:Anti-cancer Essence Formula is characterized by the synergistic effect of multi-components,multi-targets,and multi-pathways.It mainly acts on the targets of MAPK3,MAPK1,RELA,AKT1,TP53,FOS,MAPK14,RXRA,MAPK8,and EGFR through the active ingredients such as quercetin,kaempferol,β-sitosterol,and racemic carvacrol.It also regulates the signaling pathways of MAPK,Relaxin,TNF,T-cell receptor,Prolactin,and PI3K-Akt.