COX-2 inhibitor celecoxib can suppress the proliferation of FLT3-ITD positive acute myeloid leukemia cells with prominent down regulation of MEK/MCL-1 expression in vitro.
10.7534/j.issn.1009-2137.2013.04.014
- Author:
Li-Xia DU
1
;
Yong-Qian JIA
;
Wen-Tong MENG
;
Fang-Fang SHI
;
Xu-Shu ZHONG
;
Ling-Ling MA
;
Jin YUAN
;
Ji-Sha ZENG
Author Information
1. Department of Hematology & Research Laboratory of Hematology, Chengdu 610041, Sichuan Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Celecoxib;
Cell Proliferation;
drug effects;
Cyclooxygenase 2 Inhibitors;
pharmacology;
Gene Expression Regulation, Leukemic;
Humans;
K562 Cells;
Leukemia, Myeloid, Acute;
drug therapy;
metabolism;
pathology;
MAP Kinase Kinase 1;
genetics;
Myeloid Cell Leukemia Sequence 1 Protein;
genetics;
Proto-Oncogene Proteins c-akt;
genetics;
Pyrazoles;
pharmacology;
Signal Transduction;
Sulfonamides;
pharmacology;
fms-Like Tyrosine Kinase 3;
genetics
- From:
Journal of Experimental Hematology
2013;21(5):1157-1161
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of this study was to investigate the effects of Celecoxib on the proliferation of the FLT3-ITD positive and negative acute myeloid leukemia cells and its mechanism. The proliferation inhibition effect of Celecoxib with different doses on the FLT3-ITD positive cells MV4-11 and the FLT3-ITD negative K562 cells was detected by CCK-8 method, the cell apoptosis was determined by flow cytometry, and the MEK, Mcl-1, pAKT expression was tested by Western blot. The results showed that Celecoxib inhibited the proliferation of both MV4-11 and K562 cells, but the IC50 for MV4-11 was (29.14 ± 2.4) µmol/L, which was significantly lower than that of K562 cells (39.84 ± 1.0) µmol/L (P < 0.05); The induced apoptosis rate of Celecoxib at 20-80 µmol/L on MV4-11 was not observed, but there was apparent influence on K562 at the same concentration. Western blot showed that Celecoxib down-regulated the expression of MEK and Mcl-1 but did not change the expression of pAKT obviously on MV4-11 cells, while the expression of Mcl-1 was reduced a little, but no obvious change were found in the expression of MEK and pAKT on K562 cells. It is concluded that the Celecoxib can inhibit the proliferation of FLT3-ITD positive AML cells distinctly, and the potential mechanism may be related to the inhibition of the MEK/Mcl-1 signaling pathway.
