摘要
目的:运用网络药理学方法分析荜茇调控铁死亡治疗肺癌的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、Genecards数据库获得荜茇活性成分及相关靶点、肺癌相关疾病靶点并取交集靶点。通过Cytoscape 3.8.0构建“药物-成分-疾病-靶点”网络,分析其作用机制。通过String数据库构建蛋白质互作网络(protein-protein interaction networks,PPI),筛选荜茇治疗肺癌的核心靶点,通过R软件进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。通过FerrDb数据库检索调控铁死亡的基因,最终分析荜茇活性成分、肺癌和铁死亡三者之间关系。通过肿瘤基因组图谱(the cancer genome atlas,TCGA)数据库分析基因差异表达情况。结果:从TCMSP中获取荜茇有效活性成分15种,靶点158个;从GeneCards数据库获取肺癌相关基因23469个;获得荜茇治疗肺癌的关键靶点68个;从FerrDb数据库获得259个与铁死亡相关的基因;预测得到以IL-6、NOX1、NOX3、PTGS2和G6PD 5个荜茇调控铁死亡治疗肺癌的可能作用靶标,通过分析以上基因在正常与肿瘤组织表达中存在显著差异。结论:荜茇可能通过IL-6、NOX1、NOX3、PTGS2、G6PD 5个基因起到调控铁死亡治疗肺癌的作用。
Objective:To analyze the mechanism of action of Biba(Piper longum)in regulating ferroptosis in treatment of lung cancer with network pharmacology methods.Method:The active ingredients and related targets of Piper longum,as well as lung cancer related disease targets,were obtained through the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and Genecards database,and the intersection targets were selected.Construct a"drug component disease target"network through Cytoscape 3.8.0 and analyze its mechanism of action.Construct protein protein interaction networks(PPI)using a String database to screen the core targets of Piper longum for anti lung cancer.Conduct gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis using R software.Retrieve the genes regulating iron death through the FerrDb database,and ultimately analyze the relationship between the active components of Piper longum,lung cancer,and iron death.Analyze gene differential expression through the tumor genome atlas(TCGA)database.Result:15 effective active ingredients and 158 targets of Piper longum were obtained from TCMSP;Obtain 23469 lung cancer related genes from the GeneCards database;Obtaining 68 key targets for the treatment of lung cancer with piper longum;Obtain 259 genes related to iron death from the FerrDb database;We predicted that IL6,NOX1,NOX3,PTGS2,and G6PD5 may be potential targets for regulating iron death in the treatment of lung cancer with Piper longum.By analyzing the expression of these genes in normal and tumor tissues,significant differences were observed.Conclusion:Piper longum may regulate iron death in the treatment of lung cancer through five genes:IL6,NOX1,NOX3,PTGS2,and G6PD.
作者
李梦珂
常思思
高付彦
卢娟娟
李洪霖
LI Mengke;CHANG Sisi;GAO Fuyan;LU Juanjuan;LI Honglin(Henan University of Chinese Medicine,Zhengzhou Henan China 450046;The Second Affiliated Hospital to Henan University of Chinese Medicine/Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou Henan China 450002)
出处
《中医学报》
CAS
2023年第12期2582-2589,共8页
Acta Chinese Medicine
基金
国家中医临床研究基地科研专项课题项目(2021JDZX2029,2021JDZX2131)
河南省中医药科学研究专项课题项目(2022ZY2018)。
关键词
荜茇
肺癌
铁死亡
网络药理学
Biba(Piper longum)
lung cancer
ferroptosis
network pharmacology