槲皮素治疗非小细胞肺癌的网络药理学分析及细胞实验验证  

Anti-lung Cancer Mechanism of Quercetin Based on Network Pharmacology and Experimental Validation

作　　者：王翊 蒲晓芳[1,2] WANG Yi;PU Xiaofang(School of Pharmacy,Shandong University of Chinese Medicine,Ji'nan 250355,China;School of Management,Shandong University of Chinese Medicine,Ji'nan 250355,China)

机构地区：[1]山东中医药大学药学院,山东济南250355 [2]山东中医药大学管理学院,山东济南250355

出　　处：《食品工业科技》2025年第2期334-342,共9页Science and Technology of Food Industry

基　　金：山东省中医药科技项目(2020M008);山东省重点研发计划(2022TZXD0036)。

摘　　要：目的:探究槲皮素治疗非小细胞肺癌(NSCLC)的潜在机制,并结合分子生物学实验验证。方法:通过SwisTargetPrediction和DrugBank数据库筛选槲皮素的靶点,通过GeneCards、TTD数据库收集NSCLC的疾病靶点,进行靶点映射获得槲皮素治疗NSCLC的靶点,应用STRING数据库获取蛋白-蛋白相互作用(PPI)网络并进行分析,使用Cytoscape 3.7.2进行可视化;利用DAVID数据库进行靶点富集,进行基因本体论分析(GO)和京都基因与基因组百科全书分析(KEGG)。采用分子对接对核心靶点进行验证,并使用PLIP平台分析结合位点力学数据。通过细胞实验评估槲皮素对A549细胞增殖的影响,并利用qRT-PCR和Western blot对核心靶点进行验证。结果:网络药理学研究显示,槲皮素能够调控126个靶点,潜在治疗NSCLC的靶点有49个,核心通路为PI3K-Akt信号通路,核心靶点为PI3K、Akt、GSK-3β。分子对接实验初步发现,槲皮素与3个核心靶点均能产生强烈结合力。细胞实验结果显示,槲皮素低、中、高剂量组干预72 h后均能够显著抑制A549细胞的增殖活力(P<0.01),并下调PI3K、Akt、GSK-3β的mRNA表达水平(P<0.05)以及蛋白表达趋势。结论:本研究分析预测了槲皮素治疗NSCLC的潜在活性机制,通过实验验证发现槲皮素可能通过抑制PI3K/Akt/GSK-3β信号通路发挥抗癌作用。Objective:To investigate the potential mechanisms of quercetin in the treatment of non-small cell lung cancer(NSCLC)and validate them through molecular biology experiments.Methods:Target prediction for quercetin was performed using the SwissTargetPrediction and DrugBank databases,while NSCLC disease targets were collected from GeneCards and TTD databases.Target mapping was performed to identify the targets of quercetin in treating NSCLC.The protein-protein interaction(PPI)network was obtained from the STRING database and analyzed using Cytoscape 3.7.2 for visualization.Target enrichment analysis was carried out using the DAVID database,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Additionally,this study employed molecular docking to validate core targets and utilized the PLIP platform for combined analysis of binding site mechanics data.The impact of quercetin on the proliferation of A549 cells was assessed through cell experiments,and core targets were validated using qRT-PCR and Western blot.Results:Network pharmacology analysis revealed that quercetin could regulate 126 targets,with 49 potential targets for NSCLC treatment.The core pathway identified was the PI3K-Akt signaling pathway,with core targets being PI3K,Akt,and GSK-3β.Molecular docking experiments preliminarily demonstrated strong binding affinity between quercetin and the three core targets.Cellular experiments indicated that quercetin intervention in low,medium,and high doses significantly inhibited the proliferative activity of A549 cells after 72 hours(P<0.01)and downregulated the mRNA expression levels of PI3K,Akt,and GSK-3β(P<0.05),as well as protein expression trends.Conclusion:This study analyzed and predicted the potential active mechanisms of quercetin in treating NSCLC.Experimental validation suggested that quercetin might exert its anticancer effects by inhibiting the PI3K/Akt/GSK-3βsignaling pathway.

关 键 词：槲皮素 非小细胞肺癌 网络药理学 分子对接 PI3K/Akt/GSK-3β信号通路 

分 类 号：R734.2[医药卫生—肿瘤]