【摘要】 目的:观察膜结合型前列腺素E2合酶1(mPGES-1)抑制剂MK886对急性髓细胞白血病细胞株HL-60的增殖抑制作用。方法:不同浓度的MK886作用于HL-60细胞不同时间后,CCK-8测定其对HL-60细胞的增殖抑制率,流式细胞术检测HL-60细胞的凋亡情况,Western blot法检测mPGES-1、Bax、Bcl-2蛋白的表达,ELISA法检测PGE2。结果:HL-60细胞株高表达mPGES-1。MK886可时间、剂量依赖性地抑制HL-60细胞mPGES-1表达和PGE2合成,同时细胞增殖受到抑制,凋亡增加,Bax蛋白表达上调,Bcl-2表达下降。结论:MK886可抑制HL-60细胞增殖,诱导凋亡,其机制与下调mPGES-1表达、抑制PGE2合成和调控Bcl-2/Bax等有关。更多还原

【Abstract】 Objective:To investigate the effects of MK886,an inhibitor of microsomal prostaglandin E synthase-1(mPGES-1),on the proliferation of leukemia cell line HL-60.Methods:HL-60 cells were treated in vitro with MK886 by different concentration.The inhibition rates of cell growth were assayed by CCK-8 method.Cell apoptosis was analyzed by flow cytometry(FCM).The expression of mPGES-1,Bax and Bcl-2 was detected by Western blot.PGE2 was measured by ELISA.Results:mPGES-1 was over-expressed in human acute myeloid leukemia HL-60 cells.MK886 inhibited proliferation of HL-60 cells and induced apoptosis in a dose-and time-dependent manner,which may result from down-regulation of mPGES-1 expression and PGE2 synthesis.Evaluation of mediators of apoptotic signaling revealed up-regulation of Bax expression,as well as significant decreased in Bcl-2.Conclusion:MK886 inhibited proliferation and induced apoptosis of HL-60 cells by reducing mPGES-1 expression and PGE2 synthesis and regulating Bcl-2/Bax expression.更多还原