基于网络药理学和分子对接探讨莪术醇治疗肝癌的作用机制  

Research on the Mechanism of Curcumol in the Treatment of Liver Cancer Based on Network Pharmacology and Molecular Docking

作　　者：冯协和 李曼 李志浩[1] 张勇洪 陈春晓 柯昌虎[1] FENG Xiehe;LI Man;LI Zhihao;ZHANG Yonghong;CHEN Chunxiao;KE Changhu(Sinopharm Dongfeng General Hospital,Hubei University of Medicine,Shiyan 442008,China;Institute of Basic Medical Sciences,Hubei University of Medicine,Shiyan 442000,China;School of Pharmacy,Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]湖北医药学院附属国药东风总医院,十堰442008 [2]湖北医药学院基础医学院,十堰442000 [3]湖北医药学院药学院,十堰442000

出　　处：《宁夏医科大学学报》2025年第3期302-311,共10页Journal of Ningxia Medical University

基　　金：国家自然科学基金青年科学基金项目(32000609);十堰市科技局科研项目(21Y72;22Y79);“十四五”省级优势特色学科群(生物与医药)资助项目(2022BMXKQT6);武当特色中药研究湖北省重点实验室(湖北医药学院)开放课题(WDCM2022012)。

摘　　要：目的利用网络药理学和分子对接方法探讨莪术醇治疗肝癌的分子机制。方法检索中药系统药理学数据库和分析平台(TCMSP)、Swiss Target Predition和PharmMapper数据库获取莪术醇的相关靶点,采用UniProt数据库对基因名称进行校正;在GeneCards、Online Mendelian Inheritance in Man(OMIM)、Therapeutic Target Database(TTD)数据库中检索肝癌疾病的相关靶点;利用Venny 2.1.0在线软件获取药物与疾病的共有靶点;STRING数据库构建蛋白相互作用网络;DAVID数据库对靶点进行基因本体论功能富集和京都基因和基因组数据库通路富集分析;利用Cytoscape 3.8.2软件绘制药物-靶点-通路-疾病网络;使用Kaplan Meier-Plotter数据库分析核心靶点基因的表达与肝癌生存期的相关性,借助AutoDock软件对莪术醇和关键靶点进行分子对接验证。结果莪术醇可以调控92个靶点和87条通路,通过白蛋白(ALB)、表皮生长因子受体(EGFR)、胰岛素样生长因子1(IGF1)、类固醇受体辅助活化因子(SRC)、雌激素受体α(ESR1)、热休克蛋白αA1(HSP90AA1)、胱天蛋白酶-3(CASP3)、丝裂原活化蛋白激酶1(MAPK1)、B细胞淋巴瘤因子2样蛋白1(BCL2L1)、过氧化物酶体增殖物激活受体γ(PPARG)等关键靶点介导癌症通路、癌症中的蛋白多糖、肾素-血管紧张素系统(Ras)、催乳素、磷脂酰肌醇-3-激酶-丝氨酸/苏氨酸蛋白激酶(PI3K-Akt)、叉头框蛋白O类(FoxO)等信号通路对肝癌发挥治疗作用。生存期分析结果显示,ALB、EGFR、IGF1、ESR1、SRC、HSP90AA1、PPARG基因的表达量与肝癌患者的生存期均具有相关性。分子对接结果表明筛选的靶点蛋白与莪术醇具有较好的结合活性。结论莪术醇可以通过多靶点、多途径发挥治疗肝癌的作用。Objective To explore the mechanism of curcumol in the treatment of liver cancer based on network pharmacology and molecular docking.Methods The targets of curcumol were collected by using traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),Swiss Target Predition and PharmMapper,and then standardized through UniProt database.The targets of liver cancer were retrieved in GeneCards,Online Mendelian Inheritance in Man(OMIM)and Therapeutic Target Database(TTD)database.Venny 2.1.0 online software was used to obtain the common targets of drug-disease,and then the STRING database was used to draw the protein-protein interaction network.The perform gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis on the targets were carried out through DAVID database.The drug-targets-pathways-disease network was built by Cytoscape 3.8.2.The relationship between the expression of key target genes and the survival curve was analyzed using the Kaplan Meier-Plotter database,and the AutoDock platform was applied in verifying the molecular docking of curcumol and core targets.Results Curcumol could regulate 92 targets and 87 pathways to treat liver cancer,which could mediate pathways in cancer,proteoglycans in cancer,renin angiotensin system(Ras),prolactin,phosphatidylinositol-3-kinases-serine/threonine protein kinase(PI3K-Akt),forkhead box protein O(FoxO)and other signaling pathways through albumin(ALB),epidermal growth factor receptor(EGFR),insulin-like growth factors 1(IGF1),steroid receptor coactivator(SRC),estrogen receptor alpha(ESR),heat shock protein 90 kDa alpha A1(HSP90AA1),caspase-3(CASP3),mitogen-activated protein kinase 1(MAPK1),B-Cell lymphoma 2 like protein 1(BCL2L1),peroxisome proliferator-activated receptor gamma(PPARG)and other key targets.The results of survival curve analysis showed that the expression levels of ALB,EGFR,IGF1,ESR1,SRC,HSP90AA1 and PPARG were related to the survival time of liver cancer patients.Molecular docking results

关 键 词：莪术醇 肝癌 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]