期刊
ANTICANCER RESEARCH
卷 41, 期 10, 页码 4947-4955出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.15308
关键词
Osteosarcoma; thioredoxin reductase; auranofin; pulmonary metastasis
类别
资金
- JSPS KAKENHI [19K16760]
- Cancer Research Funds for Patients and Family
- Foundation for Promotion of Cancer Research in Japan
- Funds for Inohana Shougakukai
- Funds for Children's Cancer Association of Japan
- Funds for Gold Ribbon Network
- Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics
- Grants-in-Aid for Scientific Research [19K16760] Funding Source: KAKEN
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.
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.
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