The FGFR Family Inhibitor AZD4547 Exerts an Antitumor Effect in Ovarian Cancer Cells

Int J Mol Sci. 2021 Oct 6;22(19):10817. doi: 10.3390/ijms221910817.

Abstract

The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.

Keywords: AZD4547; cancer stem cells; fibroblast growth factor; fibroblast growth factor receptor; ovarian cancer.

MeSH terms

  • Animals
  • Apoptosis
  • Benzamides / pharmacology*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Piperazines / pharmacology*
  • Prognosis
  • Pyrazoles / pharmacology*
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • AZD4547
  • Benzamides
  • Piperazines
  • Pyrazoles
  • Receptors, Fibroblast Growth Factor