辛二酰苯胺异羟肟酸（SAHA）可诱导软骨肉瘤细胞系发生凋亡或自噬相关的细胞死亡。
Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated cell death in chondrosarcoma cell lines.
作者信息
Yamamoto Shunsaku, Tanaka Kazuhiro, Sakimura Riku, Okada Takamitsu, Nakamura Tomoyuki, Li Yan, Takasaki Minoru, Nakabeppu Yusaku, Iwamoto Yukihide
机构信息
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
出版信息
Anticancer Res. 2008 May-Jun;28(3A):1585-91.
BACKGROUND
Since chondrosarcoma has a high resistance to conventional chemotherapy and radiotherapy, surgical resection is currently the only effective treatment. Histone deacetylase (HDAC) inhibitor exert anticancer effects, but have not been tested in chondrosarcoma.
MATERIALS AND METHODS
We investigated the phenotypic change in chondrosarcoma cells treated with SAHA by cell viability assay, Western blot, flow cytometric analysis and electron microscopy.
RESULTS
SAHA inhibited the growth of chondrosarcoma cell lines and induced apoptosis in SW1353 with a cleaved-PARP expression and sub-G1 fragmentation according to flow cytometric analysis. On the other hand, in RCS and OUMS-27, SAHA induced autophagy-associated cell death as shown by the detection of autophagosome-specific protein and specific ultrastructural morphology in the cytoplasm. In addition, SAHA significantly inhibited tumor growth in an in vivo xenograft model.
CONCLUSION
These results suggest that SAHA might be a promising agent for performing clinically useful chemotherapy against chondrosarcomas.
背景
由于软骨肉瘤对传统化疗和放疗具有高度抗性，手术切除目前是唯一有效的治疗方法。组蛋白脱乙酰酶（HDAC）抑制剂具有抗癌作用，但尚未在软骨肉瘤中进行测试。
材料与方法
我们通过细胞活力测定、蛋白质免疫印迹、流式细胞术分析和电子显微镜研究了用伏立诺他处理的软骨肉瘤细胞的表型变化。
结果
根据流式细胞术分析，伏立诺他抑制软骨肉瘤细胞系的生长，并诱导SW1353细胞凋亡，伴有PARP裂解表达和亚G1期片段化。另一方面，在RCS和OUMS-27细胞中，伏立诺他诱导自噬相关的细胞死亡，这通过检测自噬体特异性蛋白和细胞质中特定的超微结构形态得以证实。此外，伏立诺他在体内异种移植模型中显著抑制肿瘤生长。
结论
这些结果表明，伏立诺他可能是一种有前景的药物，可用于对软骨肉瘤进行临床上有用的化疗。
Zotero 插件