MEK抑制剂联合三氧化二砷对髓系白血病细胞凋亡的研究  

Study on the effects and mechanisms of MEK inhibitor enhancing apoptosis of myeloid leukemia cells induced by As_2O_3

作　　者：许民[1] 冯玫[1] 乔振华[2] 

机构地区：[1]山西省人民医院,山西太原030012 [2]山西医科大学第二医院,山西太原030001

出　　处：《临床医药实践》2008年第10期803-805,共3页Proceeding of Clinical Medicine

摘　　要：目的:研究MEK抑制剂PD98059联合三氧化二砷(As2O3)对髓系白血病细胞凋亡的影响及其作用机制。方法:将PD98059、As2O3单独或联合作用于髓系白血病细胞系HL-60、K562细胞,用AnnexinV-FITC法检测细胞凋亡,用流式细胞术检测Bcl-2、Caspapse-3表达。结果:联合组与单用组相比,细胞凋亡率明显增高。Bcl-2在HL-60、K562细胞均高水平表达。As2O3明显抑制HL-60细胞Bcl-2表达,对K562细胞Bcl-2无明显抑制作用。单用PD98059、As2O3及两药合用在诱导HL-60、K562细胞凋亡过程中,活化caspapse-3均明显上升,两药合用较单用PD98059或As2O3活化caspapse-3明显升高。结论:PD98059联合As2O3同时抑制ERK/MAPK和Bcl-2,激活Caspase酶,对HL-60细胞有协同促凋亡效应。两药联合同时靶向作用ERK/MAPK和BCR/ABL,活化Caspase酶,协同诱导K562细胞凋亡。PD98059可增强As2O3对髓系白血病细胞的凋亡诱导作用。Objective：To elucidate the effects and mechanisms of MEK inhibitor PD98059 enhancing apoptosis of myeloid leukemia cells induced by As2O3. Methods：HL 60 and K562 cells were examined. Cell apoptosis was determined by annexinV-FITC/PI double-staining. The expression of Bcl-2 and active caspapse-3 were measured by flow cytometry. Results ：PD98059 and As2O3 in combination significantly induced apoptosis of HL-60 and K562 cells compared with either PD98059 or As203. The expression levels of BcI 2 were higher in HL-60 and K562 cells. As203 decreased Bel 2 expression in HL-60 cells,but didn＇t affect Bel 2 expression in K562 cells. Either PD98059 or As2O3 alone or PD98059 and As2O3 in combination significantly increased active caspapse-3 expression in HL-60 and K562 cells ,the combination group being more significantly increased compared with the other two groups. Conclusion ：Com- bination of PD98059 and As2O3 results in the activities of caspases and the synergistic induction of apoptosis in HL-60 cells by simultaneous targeting of the ERK/MAPK and Bel-2 pathways. As2O3 interferes with the BCR/ABL protein signal transduction, whereas PD98059 lowers the apoptotic threshold,thereby increasing the activation of caspase-3 and generating the synergistic induction of apoptosis in K562 cells. PD98059 can enhance apoptosis of myeloid leukemia cells induced by As2O3.

关 键 词：白血病 髓样 有丝分裂素激活蛋白激酶类 PD98059 三氧化二砷 细胞凋亡 

分 类 号：R733.3[医药卫生—肿瘤]