鸦胆子治疗三阴性乳腺癌的作用机制分析  

Analysis of mechanism of Brucea javanica in the treatment of triple-negative breast cancer

作　　者：张会鲜 徐永吉 赵艳艳[1] 李兰芳 ZHANG Huixian;XU Yongji;ZHAO Yanyan;LI Lanfang(Department of Clinical Pharmacy,Affiliated Hospital of Jining Medical University,Jining China)

机构地区：[1]济宁医学院附属医院临床药学科,山东济宁272000

出　　处：《山东医药》2025年第4期32-36,共5页Shandong Medical Journal

基　　金：山东省医药卫生科技发展项目(202102040505)。

摘　　要：目的基于网络药理学和分子对接分析鸦胆子治疗三阴性乳腺癌(TNBC)的潜在作用机制,为TNBC新靶点及药物的开发提供理论依据。方法通过中药系统药理学分析数据库筛选鸦胆子活性成分及靶基因,通过GeneCards、TTD和OMIM数据库筛选TNBC疾病靶基因。将鸦胆子活性成分靶基因及TNBC疾病相关靶基因取交集,利用STRING数据库构建蛋白-蛋白相互作用网络(PPI),获得鸦胆子治疗TNBC的核心靶基因。通过Metascape数据库对核心靶基因进行基因本体(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析,采用分子对接观察鸦胆子治疗TNBC的主要活性成分与核心靶基因的结合能力。结果通过TCMSP数据库筛选得到18个鸦胆子活性成分、374个靶基因,与1566个TNBC疾病相关靶基因取交集后获得鸦胆子治疗TNBC的潜在靶基因124个。PPI网络分析结果显示,鸦胆子治疗TNBC的核心靶基因有17个,分别为AKT1、TP53、EGFR、NFE2L2、PTGS2等。GO功能富集分析显示,鸦胆子治疗TNBC主要涉及对氧化应激的反应、对肽类反应、激酶活性正向调节等生物过程,碳酸盐脱水酶活性、水解酶活性、组蛋白激酶活性等分子功能,膜筏、膜微区、突触前膜的整体成分等细胞组分。KEGG通路富集分析显示,鸦胆子治疗TNBC的信号通路主要涉及铁死亡通路、肿瘤蛋白多糖通路、氮代谢等。分子对接结果显示,除MAPK14外,其余16个核心靶基因均可与鸦胆子主要活性成分稳定结合;其中TERT及TFRC与活性成分的亲和力较高。结论鸦胆子中木犀草素、鸦胆子苦醇和马钱子碱等活性成分可通过影响NFE2L2、TFR1、MMP9等靶蛋白调控铁死亡相关通路,从而发挥治疗TNBC的作用。Objective To explore the potential mechanism of Brucea javanica in the treatment of triple-negative breast cancer(TNBC)based on network pharmacology and molecular docking and to provide a theoretical basis for the de-velopment of new targets and drugs for TNBC.Methods The active ingredients of Brucea javanica were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the targets of these active ingredients were searched using the SwissTargetPrediction database.TNBC-related targets were obtained through the GeneCards,Therapeutic Target Database(TTD)and Online Mendelian Inheritance in Man(OMIM)databas-es.The active ingredient targets of Brucea javanica and triple-negative breast cancer(TNBC)-related disease targets were intersected.A protein-protein interaction(PPI)network was constructed using the STRING database to identify core thera-peutic targets of Brucea javanica against TNBC.The Metascape database was used for Gene Ontology(GO)functional en-richment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Molecular dock-ing was then employed to evaluate the binding affinity between the primary active ingredients of Brucea javanica and the core targets in TNBC treatment.Results Through the screening of the TCMSP database,18 active ingredients of Brucea javanica and 374 target genes were obtained.After taking the intersection with 1,566 target genes related to TNBC dis-ease,124 potential target genes of Brucea javanica for the treatment of TNBC were obtained.PPI network analysis re-vealed 17 core therapeutic targets of Brucea javanica against TNBC,including AKT1,tumor protein p53(TP53),epider-mal growth factor receptor(EGFR),NFE2L2,prostaglandin-endoperoxide synthase 2(PTGS2),and others.GO analysis revealed that the therapeutic effects of Brucea javanica on TNBC primarily involve the biological processes such as re-sponse to oxidative stress,response to peptides,and positive regulation of kinase activity;they were associated

关 键 词：鸦胆子 三阴性乳腺癌 网络药理学 分子对接 铁死亡 

分 类 号：R737.9[医药卫生—肿瘤]