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

  • Phytomedicine. 2026 Jul 25:157:158328. doi: 10.1016/j.phymed.2026.158328.
Xinqi Ren  1 Fan Yu  1 Hong Chen  1 Xuying Qin  1 Zhongling Qiu  1 Quanyong Luo  2
Affiliations
  • 1. Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China.
  • 2. Department of Nuclear Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai 200233, China. Electronic address: [email protected].
Abstract

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.

Keywords
Lenvatinib resistance; PDGFRB; Thyroid cancer; Wogonin.
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