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

TL;DR

This study uncovers how quercetin inhibits triple-negative breast cancer by modulating T-cell targets, using single-cell sequencing and network pharmacology to identify key interactions and pathways involved.

Contribution

It integrates single-cell RNA sequencing with network pharmacology to reveal the multi-target mechanisms of quercetin in TNBC treatment.

Findings

Quercetin interacts with 79 TNBC targets including AKT1, EGFR, MMP9.

Molecular docking shows high affinity between quercetin and GSK3B.

AKT1 and MMP9 levels correlate with patient survival.

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.