Platycodin D inhibits the malignant progression of papillary thyroid carcinoma by NF-κB and enhances the therapeutic efficacy of pembrolizumab

Drug Dev Res. 2022 May;83(3):708-720. doi: 10.1002/ddr.21902. Epub 2021 Dec 3.

Abstract

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. Studies have shown that platycodin D has several pharmacological effects like anti-inflammatory, immunomodulatory, and anti-tumor effects, while the effect and mechanism of platycodin D on PTC are still unclear. This study was designed to investigate the effects of platycodin D on PTC by a series of in vitro and in vivo experiments. The results revealed that platycodin D inhibits PTC cell viability and clonal levels and affects PTC cell cycle. Platycodin D promotes apoptosis in PTC cells. Furthermore, it inhibits the activation of NF-κB signaling pathway and affects cell growth. Platycodin D inhibits PD-L1 expression and enhances the effect of pembrolizumab on PTC cells. In conclusion, platycodin D can effectively block the progression of PTC through the NF-κB signaling pathway, accompanied by cell cycle arrest and enhanced cell apoptosis. In vitro and in vivo, platycodin D was shown to enhance pembrolizumab's sensitivity to PTC. Platycodin D is a promising monomer for therapy of PTC, providing references for future research on PTC treatment.

Keywords: NF-κB signaling pathway; papillary thyroid carcinoma; pembrolizumab; platycodin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • NF-kappa B* / metabolism
  • Saponins
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Neoplasms* / metabolism
  • Triterpenes

Substances

  • Antibodies, Monoclonal, Humanized
  • NF-kappa B
  • Saponins
  • Triterpenes
  • platycodin D
  • pembrolizumab