mPGES-1抑制剂MK886对白血病HL-60细胞周期的影响

Effect of mPGES-1 Inhibitor MK886 on Cell Cycle of Leukemia HL-60 Cells

本研究探讨膜结合型前列腺素E2合酶1(mPGES-1)抑制剂MK886对人急性髓系白血病HL-60细胞周期的作用。采用流式细胞仪分析技术、Western blot、ELISA等方法检测不同浓度MK886(10、25、50μmol/L)对HL-60细胞周期的作用及对细胞周期调控因子周期蛋白D1、mPGES-1、PGE2、Akt、P-Akt、C-MYC蛋白的影响。结果表明:与正常人外周血单个核细胞比较,G0/G1期HL-60细胞比例减少,S期比例增多。MK886作用24 h后,被阻滞于G0/G1期的细胞增多,同时细胞mPGES-1表达下调,合成PGE2减少,P-Akt、C-MYC、周期蛋白D1蛋白表达下降。结论:MK886对白血病HL-60细胞有细胞周期阻滞作用,其机制可能与抑制mPGES-1表达,减少PGE2的合成,抑制Akt磷酸化及C-MYC表达,下调周期蛋白D1表达有关。

To investigate the effect of a microsomal prostaglandin E synthase-1（mPGES-1） inhibitor MK886 on cell cycle of the human acute myeloid leukemia HL-60 cells.HL-60 cells were treated with different concentration of MK886（10,25,50 μmol/L） for 24 h.Flow cytometry,Western blot and ELISA were used to measure cell cycle,cyclin D1,mPGES-1,PGE2,Akt,P-Akt and C-MYC.The results indicated that after treated with MK886,the percentage of HL-60 cells decreased in G0/G1 phase and increased in S phase,and expressions of mPGES-1,cyclin D1,P-Akt and C-MYC and synthesis of PGE2 decreased significantly.It is concluded that MK886 can arrest HL-60 cells in G0/G1 phase,the mechanism of which is possibly associated to inhibition of mPGES-1 expression,reduction of PGE2 synthesis,suppression of Akt phospholation and C-MYC expression,down-regulation of cyclin D1 expression.