摘要
目的:通过网络药理学及分子对接,分析青蒿素抗膀胱癌潜在的分子机制。方法:利用TCMSP、HERB及SwissTargetPrediction数据库检索青蒿素的相关靶点,通过GeneCards、OMIM、PharmGKB等数据库检索膀胱癌的相关靶点。取交集得到青蒿素抗膀胱癌的潜在作用靶点。通过构建PPI网络、GO和KEGG富集分析筛选核心靶点基因、生物过程及其信号通路。利用GEPIA2、HPA及TIMER数据库分析核心靶点的表达差异及肿瘤免疫浸润。通过AutoDock Tools及PyMol对青蒿素与核心靶点进行分子对接,预测其结合活性。结果:共筛选出青蒿素抗膀胱癌的潜在作用靶点86个,核心靶点基因为细胞周期蛋白B1(Cyclin-B 1,CCNB1)、细胞周期蛋白A2(Cyclin-A 2,CCNA2)、细胞周期依赖性激酶2(Cyclin-Dependent Kinase 2,CDK2)。GO富集分析生物过程主要涉及蛋白质磷酸化、细胞增殖的正调控以及对外源刺激和代谢过程;细胞组分主要涉及与细胞周期调控和突触功能相关的成分;分子功能主要涉及与酶结合、激酶活性、底物结合及氧化还原反应。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析主要涉及癌症相关通路、病毒感染、信号转导通路、细胞分化及代谢过程等。核心靶点的差异表达分析结果显示其在肿瘤组织中表达升高,肿瘤免疫浸润结果表明其与CD8阳性T细胞(Cluster of Differentiation 8-Positive T Cell,CD8^(+)T Cell)呈正相关,与CD4阳性T细胞(Cluster of Differentiation 4-Positive T Cell,CD4^(+)T Cell)呈负相关。分子对接结果显示,青蒿素与其核心靶点蛋白均具有较好的结合活性。结论:通过网络药理学及分子对接预测了青蒿素可能通过多靶点、多途径抗膀胱癌,为其更为深入的研究提供理论依据。
Objective:To analyze the potential molecular mechanisms of artemisinin in the treatment of bladder cancer using network pharmacology and molecular docking.Methods:Targets related to artemisinin were retrieved from the TCMSP,HERB,and SwissTargetPrediction databases,while bladder cancer-related targets were obtained from the GeneCards,OMIM,and PharmGKB databases.Overlapping targets were identified as potential therapeutic targets of artemisinin against bladder cancer.Core targets,biological processes,and signaling pathways were screened through construction of a protein-protein interaction(PPI)network,Gene Ontology(GO)enrichment analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Expression differences and immune cell infiltration of core targets were analyzed using the GEPIA2,HPA,and TIMER databases.Molecular docking betweenartemisinin and core target proteins was performed using AutoDock Tools and PyMol to predict binding affinity.Results:A total of 86 potential targets of artemisinin against bladder cancer were identified,with CCNB1,CCNA2,and CDK2 recognized as core targets.GO enrichment analysis showed that the biological processes mainly involvedpositive regulation of protein phosphorylation,cell proliferation,responses to external stimuli,and metabolic processes.Enriched cellular components were related to cell cycle regulation and synaptic function,while molecular functionsprimarily involved enzyme binding,kinase activity,substrate binding,and redox regulation.KEGG pathway enrichmentsuggested involvement in cancer-associated pathways,viral infection pathways,signal transduction,cell differentiation,and metabolic processes.Differential expression analysis showed that the core targets were upregulated in tumortissues.Immune infiltration analysis revealed a positive correlation with CD8^(+)T cells and a negative correlation withCD4^(+)T cells.Molecular docking results indicated favorable binding affinity between artemisinin and its core target proteins.Conclusions:Network pharmacology and molecular docking analyses suggest that artemisinin may exert anti-bladdercancer effects via multiple targets and pathways,providing a theoretical basis for further mechanistic research.
作者
王生鹏
李晨
崔皓天
杨威鹏
王新敏
章乐
WANG Shengpeng;LI Chen;CUI Haotian;YANG Weipeng;WANG Xinmin;ZHANG Le(Shihezi University School of Medicine,Shihezi,Xinjiang 832002,China;Department of Urology,the First Affiliated Hospital of Shihezi University,Shihezi,Xinjiang 832008,China)
出处
《农垦医学》
2025年第6期491-497,512,共8页
Journal of Nongken Medicine
基金
新疆生产建设兵团科技指导计划项目(2022ZD045,2022ZD073)。
关键词
青蒿素
膀胱癌
网络药理学
分子对接
Artemisinin
Bladder cancer
Network pharmacology
Molecular docking
