title: [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].
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.
authors.affiliation: Department of Hematology & Research Laboratory of Hematology, Chengdu 610041, Sichuan Province, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Du
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Jia
authors.forename: Wen-Tong
authors.initials: WT
authors.lastname: Meng
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Shi
authors.forename: Xu-Shu
authors.initials: XS
authors.lastname: Zhong
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
authors.forename: Ji-Sha
authors.initials: JS
authors.lastname: Zeng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D048369:MAP Kinase Kinase 1 / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011720:Pyrazoles; D013449:Sulfonamides; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D051057:Proto-Oncogene Proteins c-akt; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D000068579:Celecoxib