Cuproptosis inhibits tumor progression and enhances cisplatin toxicity in ovarian cancer

FASEB J. 2025 Mar 31;39(6):e70484. doi: 10.1096/fj.202500047R.

Abstract

Cuproptosis is a novel form of regulated cell death triggered by copper ion and copper ionophore. While cuproptosis has been actively explored as a potential target for cancer therapy, its role in ovarian cancer (OC) still remains unclear. In this study, we demonstrate that cuproptosis inhibits OC cell proliferation, migration, and invasion through FDX1 regulation and suppresses tumor growth in a mouse model. We also confirm that cuproptosis enhances OC sensitivity to cisplatin treatment both in vivo and in vitro. Moreover, our findings reveal that cuproptosis affects cholesterol biosynthesis in OC cells, with cholesterol playing a crucial role in its cytotoxic effect. Taken together, our results elucidate the effect of cuproptosis in OC and suggest it as a promising therapeutic strategy.

Keywords: Elesclomol; cisplatin; cuproptosis; ovarian cancer; regulated cell death.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cholesterol / biosynthesis
  • Cisplatin* / pharmacology
  • Copper* / metabolism
  • Copper* / pharmacology
  • Disease Progression
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Cisplatin
  • Copper
  • Antineoplastic Agents
  • Cholesterol