As_2O_3治疗急性早幼粒细胞白血病的作用机制  

The Mechanism of As_2O_3 for the Treatment of Acute Promyelocytic Leukemia

作　　者：钱劲英[1,2] 梁海海[1] 王璐[1] 徐志丹[1] 于绍楠[1] 单宏丽[1] 

机构地区：[1]哈尔滨医科大学药理教研室,哈尔滨150081 [2]东北林业大学医院,哈尔滨150040

出　　处：《航空航天医学杂志》2011年第9期1034-1036,共3页Journal of Aerospace medicine

摘　　要：目的:研究三氧化二砷(As2O3)治疗M3型急性早幼粒细胞白血病(APL)的作用机制。方法:将培养的NB4细胞加入不同浓度(0.5μM,1μM,1.5μM,2μM,3μM)的As2 O3作用48 h后,采用MTT比色法观察不同浓度As2O3对NB4细胞活力的影响,用流式细胞术及Caspase-3活性检测试剂盒检测As2O3引起NB4细胞凋亡情况,用Western Blot检测As2O3对Caspase-3蛋白的作用。结果:MTT比色法结果显示,As2O3明显抑制NB4细胞增殖,且呈浓度依赖性,2μM As2O3孵育48 h NB4细胞活力下降约50%;流式细胞术结果显示,2μM As2O3作用48 h后,NB4细胞凋亡率显著增加,且以早期凋亡率增加为主(P<0.01);同时As2 O3处理后的NB4细胞Caspase-3活性明显增加,为对照组的2.2倍(P<0.01);Western Blot结果显示,As2O3显著增加Caspase-3总蛋白及其激活型cleaved-Caspase-3(p17)蛋白表达量。结论:As2O3可诱导NB4细胞凋亡,此作用与激活依赖Caspase-3的细胞凋亡通路相关,但是具体是通过何种凋亡通路,以及参与其中的信号分子需要进一步验证。Objective：To investigate the mechanism of As2O3 for the treatment of M3 type of Acute Promyeloeytic Leukemia（APL）. Methods：We chose M3 type of APL NB4 cells. Firstly, we chose the concentration which As2O3 can lead to the apoptosis of NB4 Cells by MTT assay after 48h. Then we used Flow Cytometry （FCM） and easpase -3 activity detection kit to detect the role of As2O3 in promoting the apoptosis of NB4 ceils. Finally, we detected the effect of As2O3 on easpase - 3 protein by Western Blot. Results： The results of MTT assay showed that high doze of As2O3 （ 〉0. 5 μM） inhibit the proliferation of NB4 cells obviously and the effect of As2O3 depends on its concentration. Then we decided to use 2 μM As2O3 to-conduct the following experiments. The result of FCM shows that the apoptosis proportion of NB4 cells increased conspicuously （ P 〈 0.01 ）. At the same time, the activity of caspase - 3 of NB4 cells also increased obviously and was 2. 2 times as large as the control group （ P 〈 0. 01 ）. And the results of Western Blot shows that As2O3 can increase the expression of total- Caspase -3 protein and cleaved -Caspase -3 （plT）protein conspicu- ously. Conclusions：As2O3 has an effect on inducing the apoptosis of NB4 cells in vitro and its effect is related with the activation of apoptosis which dependent on caspase - 3 protein.

关 键 词：AS2O3 急性早幼粒细胞白血病 细胞凋亡 

分 类 号：R733.7[医药卫生—肿瘤]