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

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. 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. 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. 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.