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

被引：6
作者：
Kinoshita, Hideyuki [1 ]
Shimozato, Osamu [2 ]
Ishii, Takeshi [1 ]
Kamoda, Hiroto [1 ]
Hagiwara, Yoko [1 ]
Tsukanishi, Toshinori [1 ]
Ohtori, Seiji [3 ]
Yonemoto, Tsukasa [1 ]
机构：
[1] Chiba Canc Ctr, Dept Orthoped Surg, Chiba, Japan
[2] Chiba Canc Ctr Res Inst, Lab Oncogen, Chiba, Japan
[3] Chiba Univ, Grad Sch Med, Dept Orthoped Surg, Chiba, Japan
来源：
ANTICANCER RESEARCH | 2021年 / 41卷 / 10期
关键词：
Osteosarcoma; thioredoxin reductase; auranofin; pulmonary metastasis; CELLS;
D O I：
10.21873/anticanres.15308
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：4947 / 4955
页数：9
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