浙江中医药大学学报2026，Vol.50Issue(5)：530-540,549,12.DOI:10.16466/j.issn1005-5509.2026.05.002
基于网络药理学探讨槲皮素靶向NOX4抗非小细胞肺癌的作用机制
Exploring the Mechanism of Quercetin Targeting NOX4 Against Non-Small Cell Lung Cancer Based on Network Pharma-cology
摘要
Abstract
[Objective]To explore the potential targets of quercetin against non-small cell lung cancer(NSCLC)based on network pharmacology,and to validate its effects on the proliferation,migration and invasion of NSCLC cells.[Methods]The Swiss Target Prediction and Similarity Ensemble Approach(SEA)databases were used to screen potential targets of quercetin.The NSCLC-related targets were obtained from The Human Gene Database(GeneCards).Transcriptomic data of lung cancer and adjacent tissues from the Gene Expression Omnibus(GEO)database were integrated to identify common targets between quercetin and NSCLC,and construct Venn diagram.The enrichment analyses,including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses,were performed by using the Metascape and SangerBox platforms.Molecular docking was conducted by using AutoDock Vina 1.5.7 software,and molecular dynamics(MD)simulations were employed to assess the binding stability of quercetin with the target protein.The Tumor Immune Estimation Resource(TIMER)and Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were utilized to analyze the expression characteristics and prognostic relevance of key target proteins in lung cancer patients.Western blot and immunofluorescence were used to detect the effects of quercetin on target protein expression and the relevant signaling pathway.Cell counting kit-8(CCK-8)and colony formation assays were performed to evaluate the effect of quercetin on NSCLC cell proliferation,while scratch wound healing and Transwell assays were used to assess cell migration and invasion capabilities.[Results]Network pharmacology and bioinformatics analyses revealed 26 common potential targets associated with quercetin and lung cancer.Swiss Target Prediction database analysis indicated that NADPH oxidase 4(NOX4)was the most likely potential target of quercetin.The KEGG and GO enrichment analyses suggested that quercetin may regulate NSCLC through phosphatidylinositol 3-kinase-protein kinase B(PI3K-AKT)signaling pathway.Molecular docking and molecular dynamics simulations confirmed that quercetin stably binded to the NOX4 protein.Western blot demonstrated that NOX4 was highly expressed in lung cancer tissues and was significantly associated with poor prognosis in NSCLC patients,along with bioinformatic analysis.Cellular experiments further demonstrated that quercetin significantly downregulated NOX4 protein expression in H1975 and PC9 cells.Compared with control group,both low and high-dose quercetin treatments significantly inhibited the phosphorylation levels of key proteins PI3K and AKT in PI3K-AKT signaling pathway and effectively reduced cell proliferation,migration and invasion.[Conclusion]Quercetin suppresses the malignant biological behaviors of NSCLC cells by targeted downregulating NOX4 expression and inhibiting the activation of PI3K-AKT signaling pathway.关键词
槲皮素/非小细胞肺癌/NOX4/网络药理学/PI3K-AKT信号通路/分子动力学模拟Key words
quercetin/NSCLC/NOX4/network pharmacology/PI3K-AKT signaling pathway/molecular dynamics simulation分类
医药卫生引用本文复制引用
魏友煜,姚奏英,戴梦圆,纪建松,官碧华,王一帆,翁巧优,杨阳,吴兵,方世记,郑丽云,贾丽秋..基于网络药理学探讨槲皮素靶向NOX4抗非小细胞肺癌的作用机制[J].浙江中医药大学学报,2026,50(5):530-540,549,12.基金项目
浙江省医药卫生科技计划项目(2025KY1958) （2025KY1958）
浙江省自然科学基金重点项目(LLSSZ25H280002) （LLSSZ25H280002）
浙江省中医药管理局重点项目(GZY-KJS-ZJ-2025-065) Zhejiang Medical and Health Science and Technology Plan Project(2025KY1958) （GZY-KJS-ZJ-2025-065）
Key Project of Zhejiang Provincial Natural Science Foundation(LLSSZ25H280002) （LLSSZ25H280002）
Key Project of Zhejiang Provincial Administration of Traditional Chinese Medicine(GZY-KJS-ZJ-2025-065) （GZY-KJS-ZJ-2025-065）
