Quercetin suppresses the progression of HBV-associated hepatocellular carcinoma by modulating the EGFR signaling pathway

Cancer research · Hepatocellular carcinoma · EGFR · osimertinib

Quercetin inhibits the growth and migration of HBV-associated hepatocellular carcinoma by targeting EGFR, leading to downstream suppression of the PI3K/AKT/GSK3B pathway and reversal of EMT.

Background: Quercetin, a flavonoid present in many plants, shows therapeutic potential against hepatocellular carcinoma (HCC). Its specific mechanism in HBV-associated HCC (HBV-HCC) is unclear. Methods: Integrated in vitro and in vivo models were employed, assessing quercetin effects on HCC cell viability, proliferation, clonogenicity, and migration via CCK-8, EdU, colony formation, and scratch assays. Network pharmacology and molecular docking identified potential quercetin targets. Lentiviral transfection constructed HCC lines overexpressing HBx and EGFR; signaling pathways were confirmed via Western blot. A xenograft mouse model evaluated therapeutic efficacy, including combination with EGFR inhibitor osimertinib. Results: Target network analysis identified 29 therapeutic targets, with EGFR as the principal target. Docking showed EGFR and GSK3β binding affinity. In vitro studies revealed quercetin dose‑dependently suppresses EGFR, attenuates PI3K/AKT/GSK3β signaling, and reverses EMT, reducing growth and migration of HBV-HCC cells. In vivo studies with EGFR inhibitors further validated quercetin’s anti‑tumor effects through EGFR targeting and EMT suppression. Conclusion: Quercetin demonstrates therapeutic effectiveness in inhibiting HBV-HCC by targeting EGFR, thereby suppressing PI3K/AKT/GSK3β signaling, reversing EMT, and impeding progression. This provides a novel basis for targeted HBV‑HCC therapy with quercetin.

This research validates the therapeutic effectiveness of quercetin in inhibiting HBV‑HCC and elucidates the molecular mechanisms responsible for its action.

Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

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