基于数据挖掘及网络药理学技术探讨白术-党参治疗胃癌的作用机制

The action mechanism of Baizhu-Dangshen in the treatment of gastric cancer based on data mining and network pharmacology

目的:本研究拟通过数据挖掘探究中药治疗胃癌的基本规律,并利用网络药理学方法分析高频药对治疗胃癌的作用机制。方法:检索中文数据库中国知网中有关于中药治疗胃癌的文献,通过频数统计、关联规则分析、聚类分析探究中药治疗胃癌的基本规律。通过网络公开数据库筛选出中药的有效成分和潜在靶点及胃癌的相关基因,用R 4.2.2得到二者的交集基因,并利用Cytoscape 3.8.0完成有效成分-靶点-胃癌的可视化分析。在STRING数据库中构建蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络图,并用Cytoscape 3.8.0进行拓扑分析,得到核心靶点,使用R 4.2.2进行基因本体论(GO)生物富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,最后运用AutoDock 1.5.7(vina)完成药物成分和靶点的分子对接。结果:数据挖掘认为白术-党参是中药治疗胃癌的高频药对,通过网络药理学筛选出白术-党参与胃癌相关的交集基因有94个,涉及21种有效成分,其中木犀草素为主要有效成分,通过拓扑分析得出雌激素受体(Estrogen Receptor,ESR)1、热休克蛋白90α家族A类成员1(Heat Shock Protein 90 Alpha Family Class A Member 1,HSP90AA1)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)14、丝氨酸/苏氨酸蛋白激酶(Akt Serine/Threonine Kinase,AKT)1、MAPK1、视网膜母细胞瘤基因(Retinoblastomal,RB1)和肿瘤蛋白p53(Tumor Protein p53,TP53)可能是治疗胃癌的关键靶点。GO生物富集分析共产生2011个条目,包括生物过程1796项、细胞组成78项和分子功能137项,通过KEGG通路富集分析筛选出163条通路。分子对接结果表明核心靶点均与木犀草素具有较强的结合活性。结论:本研究初步揭示了白术-党参通过多成分、多靶点、多通路治疗胃癌的作用机制,及其药物成分和靶点有较强的结合力。

Objective:This study aims to explore the basic rules of TCM medicine in the treatment of gastric cancer through data mining,and analyze the mechanism of action of high-frequency drugs in the treatment of gastric cancer by network pharmacology.Methods:Literature on TCM treatment of gastric cancer in China National Knowledge Infrastructure(CNKI)was searched to explore the basic rules of TCM treatment of gastric cancer through frequency statistics,association rule analysis and cluster analysis.The active ingredients of TCM,potential targets and gastric cancer-related genes were screened out through the online public database.The intersection genes of the two were obtained using R 4.2.2,and visual analysis of active ingredients-targets-gastric cancer was completed by Cytoscape 3.8.0.The protein-protein interaction(PPI)network diagram was constructed in STRING database,and the core target was obtained by topological analysis with Cytoscape 3.8.0.Enrichment analysis of GO(Gene Ontology)biology and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway were performed by R 4.2.2.Finally,AutoDock 1.5.7(vina)was used to complete the molecular docking of drug ingredients and targets.Results:Through data mining,it was concluded that Baizhu(Atractylodes Macrocephala Koidz)-Dangshen(Codonopsis Radix)was a high-frequency drug pair for the treatment of gastric cancer with TCM medicine,and 94 intersection genes of Baizhu-Dangshen involved in gastric cancer were screened out by network pharmacology,involving 21 active ingredients,of which luteolin was the main active ingredient.Through topological analysis,ESR1,HSP90AA1,MAPK14,AKT1,MAPK1,RB1 and TP53,which may be the key targets for the treatment of gastric cancer,were screened out.GO bioconcentration analysis yielded a total of 2011 entries,including 1796 items for biological processes,78 items for cell composition,and 137 items for molecular function.A total of 163 pathways were screened out by KEGG pathway enrichment analysis.The results of molecular docking showed that the core targets had strong binding activity with luteolin.Conclusion:This study preliminarily reveals the mechanism of action of Baizhu-Dangshen in the treatment of gastric cancer through multi-ingredient,multi-target and multi-pathway,and the strong binding power of its drug ingredients and targets.