Antitumor and resensitizing effects of wogonin in thyroid cancer via PDGFRB-dependent mechanisms.

BACKGROUND: Wogonin, a bioactive flavonoid from Scutellaria baicalensis Georgi, exhibits broad-spectrum anticancer effects. However, whether wogonin exerts antitumor effects in thyroid cancer (TC) or reverses drug resistance remains unknown.

METHODS: The antitumor effects of wogonin were evaluated in thyroid cancer cells and in xenograft models. RNA-sequencing, molecular docking, molecular dynamics, cellular thermal shift assay, and surface plasmon resonance were used to identify molecular targets. Lenvatinib-resistant cells were established to investigate the potential of wogonin in reversing acquired resistance.

RESULTS: Wogonin inhibited TC cell proliferation, induced apoptosis and suppressed tumor growth in a dose-dependent manner. Biophysical and computational methods showed that wogonin binds to the extracellular domain of the platelet-derived growth factor receptor beta (PDGFRB), leading to its downregulation and inactivation of the PI3K/AKT pathway. Furthermore, PDGFRB overexpression was associated with acquired lenvatinib resistance, and wogonin contributed to resensitization to lenvatinib by reducing PDGFRB.

CONCLUSION: Wogonin exerts remarkable antitumor effects against TC by binding to PDGFRB, leading to its downregulation, and subsequently suppressing the PI3K/AKT pathway. Furthermore, PDGFRB upregulation contributes to lenvatinib resistance in TC, while wogonin partially reverses this resistance in a PDGFRB-dependent manner.