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

Abstract

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

CLC Number:

965.2

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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