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金诺芬与塞来昔布联合抑制局部滑膜肉瘤进展。

The Combination of Auranofin and Celecoxib Suppresses Local Synovial Sarcoma Progression .

机构信息

Department of Orthopedic Surgery, Chiba Cancer Center, Chiba, Japan;

Laboratory of Oncogenomics, Chiba Cancer Center Research Institute, Chiba, Japan.

出版信息

Anticancer Res. 2024 Jun;44(6):2453-2458. doi: 10.21873/anticanres.17052.

Abstract

BACKGROUND/AIM: Synovial sarcoma (SS) is a rare malignant tumor with a poor survival rate. We previously reported that a combination of auranofin (AUR), a thioredoxin reductase inhibitor, and celecoxib (CE), an anti-inflammatory drug, significantly impedes the local progression of osteosarcoma (OS). However, the role of redox regulation in SS remains to be elucidated. This study aimed to investigate the efficacy of combined treatment of AUR and CE on the local progression of SS in vivo.

MATERIALS AND METHODS

Nu/nu mice were implanted with the human SS cell line, Aska-SS, and treated with vehicle control, AUR, or a combination of AUR and CE (AUR-CE). Primary tumor size and weight were evaluated for the study duration and upon resection, respectively. Hematoxylin and eosin (H&E) and Ki-67 staining were performed to assess the local progression of SS.

RESULTS

A statistically significant reduction in tumor size and weight was observed in the AUR- and AUR-CE-treated groups upon excision compared to that in the vehicle-treated group. The AUR-CE-treated group showed synergistic inhibition of local tumor growth. H&E staining of local SS tumors revealed decreased cell density and nuclear deformation in the AUR- and AUR-CE-treated groups compared to those in the vehicle-treated group. Immunohistochemical staining revealed a statistically significant decrease in Ki-67-positive cells in the AUR-CE-treated group compared to the vehicle-treated group.

CONCLUSION

The combination of AUR and CE showed significant potential for delaying the local progression of SS. These findings support the repurposing of AUR and CE as early treatment options for SS.

摘要

背景/目的:滑膜肉瘤(SS)是一种罕见的恶性肿瘤,生存率低。我们之前报道过,硫氧还蛋白还原酶抑制剂金诺芬(AUR)和抗炎药塞来昔布(CE)的联合应用显著抑制了骨肉瘤(OS)的局部进展。然而,氧化还原调节在 SS 中的作用仍有待阐明。本研究旨在探讨 AUR 和 CE 联合治疗对体内 SS 局部进展的疗效。

材料和方法

Nu/nu 小鼠植入人 SS 细胞系 Aska-SS,并给予载体对照、AUR 或 AUR 和 CE(AUR-CE)的联合治疗。在研究期间和切除时分别评估原发肿瘤的大小和重量。进行苏木精和伊红(H&E)和 Ki-67 染色以评估 SS 的局部进展。

结果

与载体处理组相比,AUR 和 AUR-CE 处理组在切除时肿瘤大小和重量均显著减小。AUR-CE 处理组显示出协同抑制局部肿瘤生长的作用。与载体处理组相比,AUR 和 AUR-CE 处理组局部 SS 肿瘤的 H&E 染色显示细胞密度降低和核变形。免疫组织化学染色显示,AUR-CE 处理组 Ki-67 阳性细胞数与载体处理组相比显著减少。

结论

AUR 和 CE 的联合应用显示出显著延缓 SS 局部进展的潜力。这些发现支持将 AUR 和 CE 重新用作 SS 的早期治疗选择。

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