DuP-697对K562白血病细胞凋亡诱导作用观察及机制研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (9): 1016-1022.

DuP-697对K562白血病细胞凋亡诱导作用观察及机制研究

刘冀衡, 曹永清

长沙市第一医院血液肿瘤科,长沙410011,湖南

收稿日期:2010-03-22 修回日期:2010-08-16 出版日期:2010-09-26 发布日期:2020-09-17
通讯作者: 曹永清,女,本科,副主任医师,研究方向:慢性粒细胞白血病的治疗。Tel: 13055188180, E-mail: 461179016@qq.com
作者简介:刘冀衡 ,男,硕士,主治医师,研究方向:慢性粒细胞白血病的治疗。Tel: 13507417483, E-mail: liujiheng76@163.com

Effects and mechanism of COX-2 inhibitor-DuP-697 in inducing K562 Cells apoptosis

LIU Ji-heng, CAO Yong-qing

Department of Tumor,the First Hospital of Changsha,Changsha 410011, Hunan, China

Received:2010-03-22 Revised:2010-08-16 Online:2010-09-26 Published:2020-09-17

摘要/Abstract

摘要： 目的: 观察选择性COX-2抑制剂DuP-697对慢粒白血病K562细胞的凋亡诱导效应,并探讨其作用机制。方法: 细胞培养加入DuP-697作用后,透射电镜观察细胞凋亡的形态,流式细胞仪检测细胞周期和凋亡率,Western印迹检测K562细胞Caspase-8蛋白表达;用Z-IETD-FMK阻断Caspase-8活性,以证实Caspase-8蛋白表达和细胞凋亡的关系。结果: DuP-697能诱导K562细胞凋亡,其作用呈浓度依赖性,这一效应与Caspase-8蛋白表达上调和裂解激活有关; 用Z-IETD-FMK阻断Caspase-8的活性,细胞凋亡明显受抑。结论: DuP-697能诱导K562细胞凋亡,其机制涉及Caspase-8活化的信号转导途径。

关键词: DuP-697, 慢性粒细胞白血病, K562细胞, 凋亡, 机制

Abstract: AIM: To invetigate the effect of DuP-697, a selective COX-2 inhibitor, on human chronic myeloid leukemia (CML) cell line K562, and further explore its molecular mechanism.METHODS: After incubating K562 cells with increasing doses of DuP-697 in vitro, the morphological changes of cells were observed by transmission electron microscope, and the modification of cell cycle distribution and the rate of apoptotic cells were analyzed by flow cytometry.Western blot was used to evaluate the effect of DuP-697 on the Caspase-8 expression level in K562 cells. Z-IETD-FMK, a specific inhibitor of Caspases-8, was applied to further investigate the role of Caspase-8 in DuP-697-induced apoptosis in K562 cells.RESULTS: DuP-697 induced apoptotic cell death in K562 cells in a concentration-dependent manner in vitro, which was associated with up-regulation and activation (cleavage) of Caspase-8. When K562 cells were pretreated with Z-IETD-FMK, the ability of DuP-697 in inducing K562 cell death was obviously abrogated by this compound.CONCLUSION: These data indicat that DuP-697 induces apoptotic cell death in human CML K562 cells partially through the Caspase-8-mediated pathway.

Key words: DuP-697, Chronic myelocytic leukemia , K562 cells, Apoptosis, Mechanism

中图分类号:

965.2

刘冀衡, 曹永清. DuP-697对K562白血病细胞凋亡诱导作用观察及机制研究[J]. 中国临床药理学与治疗学, 2010, 15(9): 1016-1022.

LIU Ji-heng, CAO Yong-qing. Effects and mechanism of COX-2 inhibitor-DuP-697 in inducing K562 Cells apoptosis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(9): 1016-1022.

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