The Thioredoxin Reductase Inhibitor Auranofin Suppresses Pulmonary Metastasis of Osteosarcoma, But Not Local Progression

Anticancer Res. 2021 Oct;41(10):4947-4955. doi: 10.21873/anticanres.15308.

Abstract

Background/aim: Auranofin (AUR), a thioredoxin reductase (TXNRD) inhibitor, shows anticancer activity against several cancers. This study investigated the effects of AUR on the local progression and pulmonary metastasis of osteosarcoma (OS).

Materials and methods: Publicly available expression cohorts were analysed to study the relationship between TXNRD-2 expression and the survival of patients with OS. The murine OS cell line LM8 was stimulated with AUR. Cell viability, apoptosis-related protein levels, caspase activity, and wound healing were analysed. Tumor progression and pulmonary metastasis were investigated in C3H mice implanted with LM8 cells.

Results: High-level expression of TXNRD-2 represented a negative prognostic factor for metastasis and overall survival in patients with OS. AUR induced apoptosis of OS cells via the oxidative stress-MAPK-Caspase 3 pathway, and suppressed the migration of OS cells. AUR inhibited the pulmonary metastasis of OS, but not local progression.

Conclusion: AUR represents a potential therapeutic drug for suppressing pulmonary metastasis of OS.

Keywords: Osteosarcoma; auranofin; pulmonary metastasis; thioredoxin reductase.

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Apoptosis
  • Auranofin / pharmacology*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred C3H
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Prognosis
  • Survival Rate
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antirheumatic Agents
  • Auranofin
  • Thioredoxin-Disulfide Reductase