COX-2抑制剂塞来昔布对FLT3-ITD突变阳性急性髓系白血病细胞体外增殖的影响及其机制研究  

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

作　　者：杜丽霞[1] 贾永前[1] 孟文彤[2] 石芳芳[1] 钟旭姝[1] 麻亮亮[1] 袁进[1] 曾继莎[1] 

机构地区：[1]四川大学华西医院血液内科,四川成都610041 [2]四川大学华西医院干细胞生物学研究室,四川成都610041

出　　处：《中国实验血液学杂志》2013年第5期1157-1161,共5页Journal of Experimental Hematology

摘　　要：本研究旨在探讨塞来昔布(Celecoxib)对FLT3-ITD突变阳性急性髓系白血病细胞增殖、凋亡的影响及其机制。以不同浓度Celecoxib作用于MV4-11(FLT3-ITD+),K562(FLT3-ITD-)细胞,通过CCK-8法检测白血病细胞增殖抑制率,流式细胞术检测白血病细胞凋亡,Western blot法检测MEK,Mcl-1,pAkt蛋白的表达。结果表明,Celecoxib对白血病细胞MV4-11,K562细胞的增殖均有抑制作用,其对MV4-11细胞增殖抑制的IC50为(29.14±2.4)μmol/L,显著低于K562细胞的IC50浓度(39.84±1.0)μmol/L,两者差异有统计学意义(P<0.05);以20-80μmol/L浓度范围的Celecoxib作用于MV4-11细胞未观察到细胞发生明显凋亡,而同等浓度范围的Celecoxib作用于K562细胞可见凋亡率随药物浓度的增加而增高;Western blot结果显示,IC50浓度的Celecoxib作用MV4-11细胞后可明显下调MEK,Mcl-1的表达,对pAKT的表达未见明显影响,而作用K562细胞后对Mcl-1的表达轻微下调,对MEK,pAkt未见明显影响。结论:Celecoxib能够显著抑制FLT3-ITD突变阳性AML细胞的增殖,其作用机制可能与抑制MEK/Mcl-1信号通路有关。The purpose of this study was to investigate the effects of Celecoxib on the proliferation of the FLT3-1TD positive and negative acute myeloid leukemia cells and its mechanism. The proliferation inhibition effect of Celecoxib with different doses on the FLT3-1TD positive cells MV4-11 and the FLT3-1TD 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 ICs0 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 expres- sion 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 FLT3-1TD positive AML cells distinctly, and the potential mechanism may be related to the inhibition of the MEK/Mcl-1 signaling pathway.

关 键 词：COX-2抑制剂 FLT3-ITD MV4-11 K562 

分 类 号：R733.71[医药卫生—肿瘤] R979.1[医药卫生—临床医学]