Anti-tumor effect by non-steroidal anti-inflammatory drugs

非甾体抗炎药的抗肿瘤作用

• 批准号: 13670800
• 负责人: ADACHI Souichi
• 金额: $ 1.92万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670800/
• 关键词: NSAID; Apoptosis; Mitochondria; Anti-tumor effect; CLL; Neuroblastoma; CLL; カスパーゼ; 慢性リンパ性白血病

We have been reported that etodolac, a chiral non-steroidal anti-inflammatory drug (NSAID) was shown to be pro-apoptotic in primary CLL cells both in vitro and in vivo. Here we also show anti-tumor effect of both the R and S-enatiomers of etodolac against several cancers including neuroblastoma cell line and primary CML cells. Etodolac has additive cytotoxic effects from combinations with other chemotherapeutic drugs such as cyclophosphamide and vincristine. The mechanism of cell death is mitochondrial-dependent pathway because we show that (1) dysfunction of mitochondrial oxygen uptake and membrane potential (2) activation of caspase 9 and caspase 3 (3) degradation of Mcl-1

依托度酸是一种手性非甾体类抗炎药，在体外和体内均能诱导原代CLL细胞凋亡。在这里，我们还显示了依托度酸的R和S-对映体对多种癌症（包括神经母细胞瘤细胞系和原代CML细胞）的抗肿瘤作用。依托度酸与其他化疗药物（如环磷酰胺和长春新碱）联合使用时具有额外的细胞毒性作用。细胞死亡的机制是线粒体依赖性途径，因为我们发现：（1）线粒体氧摄取和膜电位功能障碍;（2）caspase 9和caspase 3激活;（3）Mcl-1降解

项目成果

足立 壮一: "血液疾患とアポトーシス"小児内科. 34巻12号. 1803-1807 (2002)

Soichi Adachi：“血液疾病和细胞凋亡”，第 34 卷，第 12 期。1803-1807 (2002)

Souichi Adachi: "Apoptosis induced by molecular targeting therapy in hematological malignancies"Acta Haematologica. 111. 107-123 (2004)

Souichi Adachi：“血液恶性肿瘤中分子靶向治疗诱导的细胞凋亡”Acta Haematologica。

足立 壮一: "血液疾患とアポトーシス"小児内科. 34. 1803-807 (2002)

Soichi Adachi：“血液疾病和细胞凋亡”小儿内科 34. 1803-807 (2002)。

souichi Adachi: "Apoptosis in hematological malignancy"Japanese Journal of Pediatric Medicine. 34. 1803-1807 (2002)

Souichi Adachi：“血液恶性肿瘤中的细胞凋亡”日本儿科医学杂志。