摘要
目的通过网络药理学、分子对接和实验验证的方法探讨汉黄芩素抗非小细胞肺癌的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)和SwissTargetPrediction数据库挖掘汉黄芩素的作用靶点;采用GeneCards、TTD和DrugBank数据库收集与非小细胞肺癌相关的靶点,并取两者的重叠靶点。使用STRING数据库分析靶点间的蛋白-蛋白互作(PPI)关系,并通过Cytoscape软件进行可视化和拓扑分析,筛选出关键靶点。使用R软件中的clusterProfiler包对重叠靶点进行GO功能和KEGG通路富集分析。采用AutoDockTools 1.5.6软件对关键靶点与汉黄芩素进行分子对接验证。通过体外细胞实验探讨汉黄芩素抗非小细胞肺癌的潜在机制。结果共获得44个汉黄芩素与非小细胞肺癌的共同靶点,PPI网络发现Akt1、TP53和JUN为关键治疗靶点。GO功能富集分析发现,共同靶点主要与活性氧代谢过程的调节、蛋白激酶调节活性等过程相关。KEGG通路富集分析表明,汉黄芩素抗非小细胞肺癌与PI3K-Akt、IL-17、p53等信号通路有关。分子对接结果表明,汉黄芩素与Akt1、TP53、JUN具有较好的结合能力。此外,细胞实验证实,汉黄芩素处理能有效抑制A549细胞的增殖、迁移和侵袭,促进细胞凋亡。Western Blot分析结果显示,汉黄芩素作用A549细胞后,p-Akt、TP53和JUN的表达水平下调(P<0.05)。结论汉黄芩素能够通过调节PI3K-Akt、IL-17、p53等信号通路发挥抗非小细胞肺癌的作用,其作用机制与调节Akt1、TP53、JUN靶点有关。
Objective The mechanism of wogonin against non-small cell lung cancer(NSCLC)was explored by network pharmacology,molecular docking and experimental verification.Methods The targets of wogonin were mined using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP)and SwissTargetPrediction databases,and the targets related to NSCLC were retrieved from the GeneCards,TTD,and DrugBank databases.An intersection analysis was performed to identify shared targets,which were then analyzed for protein-protein interaction(PPI)using the STRING database.The Cytoscape software was utilized for visualization and topological analysis,and the key targets were screened.The clusterProfiler package in R software was used to conduct GO function annotation and KEGG pathway enrichment analysis.The AutoDockTools1.5.6 software was employed to verify the molecular docking between key targets and wogonin.In vitro experiments were conducted to investigate the potential mechanisms of wogonin against NSCLC predicted by network pharmacology.Results A total of 44 common targets of wogonin and NSCLC were obtained.Through PPI network analysis,Akt1,TP53,and JUN were the key therapeutic targets.GO function enrichment analysis revealed that the 44 common targets were primarily associated with the regulation of reactive oxygen species metabolic process,and protein kinase regulator activity.KEGG pathway enrichment analysis showed that the anti-NSCLC activity of wogonin was related to the PI3K-Akt,IL-17,and p53 signaling pathways.Molecular docking results demonstrated that wogonin had good binding ability with Akt1,TP53,and JUN.In addition,cell experiments confirmed that wogonin treatment could effectively inhibit the proliferation,migration and invasion of A549 cells and promote apoptosis.Western Blot analysis showed that the expression levels of p-Akt,TP53 and JUN were downregulated after A549 cells were treated with wogonin(P<0.05).Conclusion Wogonin exerts anti-NSCLC effects by regulating PI3K-Akt,IL-17,p53 and other signaling pathways,and its mechanism of action is related to the regulation of Akt1,TP53,JUN targets.
作者
吴轲
陈思琦
姜晨晨
伊晓娇
朱俊峰
WU Ke;CHEN Siqi;JIANG Chenchen;YI Xiaojiao;ZHU Junfeng(College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053 Zhejiang,China;Department of Pharmacy,Zhejiang Cancer Hospital,Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310022 Zhejiang,China;Department of Pharmacy,Hangzhou Xixi Hospital,Hangzhou 310023 Zhejiang,China)
出处
《中药新药与临床药理》
北大核心
2025年第3期416-424,共9页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金青年项目(82003920)
浙江省自然科学基金项目(LQ24H280003)
浙江省中医药科技计划项目(2021ZB040,2023ZR043)。
