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

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.

Automated summary

High-level expression of TXNRD-2 is a negative prognostic factor for metastasis and overall survival in osteosarcoma patients. Auranofin induces apoptosis of osteosarcoma cells via the oxidative stress-MAPK-Caspase 3 pathway and suppresses cell migration. Auranofin inhibits pulmonary metastasis of osteosarcoma, but not local progression.