Mechanism of Quercetin in Inhibiting Triple-Negative Breast Cancer by Regulating T Cell-Related Targets: An Analysis Based on Single-Cell Sequencing and Network Pharmacology

Abstract

Objective: To investigate the mechanism by which quercetin inhibits triple-negative breast cancer (TNBC) through regulating T-cell-related targets, providing a novel strategy for TNBC immunotherapy.Methods: Single-cell RNA sequencing (GSE161529 dataset) and network pharmacology were integrated. PCA and UMAP clustering identified T-cell subsets and differentially expressed genes in TNBC microenvironment. TNBC-related targets were screened via CTD and OMIM databases, with functional pathways analyzed by GO/KEGG enrichment. Molecular docking and PPI networks validated interactions between quercetin and core targets.Results: Quercetin intersected with 79 TNBC targets, including AKT1, EGFR, and MMP9, enriched in EGFR inhibitor resistance and endocrine resistance pathways. Molecular docking revealed the highest affinity between quercetin and GSK3B (-13.2 kJ/mol). AKT1 and MMP9 expression correlated with patient survival.Conclusion: Quercetin may reverse TNBC immunosuppression by multi-target modulation of T-cell function, but clinical application requires solutions for its low bioavailability, such as delivery systems or combination therapies.