二硫化二砷对维甲酸耐药急性早幼粒细胞白血病细胞株NB4-R2增殖和凋亡的影响  

Influence of As_2S_2 on proliferation and apoptosis of ATRA-resistant acute promyelocytic leukemia cell line NB4-R2

作　　者：雷秦 

机构地区：[1]陕西省核工业二一五医院血液科,陕西西安712000

出　　处：《现代肿瘤医学》2015年第19期2734-2737,共4页Journal of Modern Oncology

摘　　要：目的:研究As2S2对维甲酸耐药急性早幼粒细胞白血病细胞株NB4-R2增殖和凋亡的影响,并探讨其机制。方法:CCK-8法检测不同浓度As2S2作用于NB4-R2细胞24、48和72h对细胞的生长抑制率,计算半数抑制浓度(IC50),Annexin V-FITC/PI双染法检测As2S2对NB4-R2细胞凋亡的影响,实时定量PCR(quantitative real-time PCR,qRT-PCR)和Western blot检测As2S2作用前后NB4-R2细胞PML-RARα融合基因和融合蛋白的表达水平。结果:不同浓度As2S2分别作用于NB4-R2细胞24、48和72h后,细胞增殖均受到不同程度抑制,且该抑制作用呈时间和剂量依赖性,As2S2对NB4-R2细胞的IC50分别为(17.64±2.11)μmol/L、(8.57±1.03)μmol/L和(5.82±0.71)μmol/L。流式细胞术结果表明As2S2处理24、48和72h后细胞凋亡率分别为正常对照组的(4.43±0.12)倍、(6.50±0.09)倍和(8.63±0.36)倍。qRT-PCR结果表明PML-RARαmRNA表达水平较作用前分别降低了(1.47±0.09)倍、(2.86±0.82)倍和(7.46±1.09)倍,同时,PML-RARα融合蛋白表达水平较作用前分别降低了(1.36±0.16)倍、(1.85±0.33)倍和(3.99±0.63)倍(P<0.05)。结论:As2S2可显著抑制NB4-R2细胞增殖并促进细胞凋亡,其机制与诱导PML-RARα融合基因和融合蛋白降解密切相关。Objective：To explore the effect and mechanism of As2 S2 on proliferation and apoptosis of ATRA - re-sistant acute promyelocytic leukemia cell line NB4 - R2. Methods：The growth inhibition rate of As2 S2 on NB4 - R2 was detected by CCK - 8 kit. The apoptosis ratio was detected by Annexin V - FITC/ PI. The expression of PML -RARα fusion gene and protein were detected by quantitative real - time PCR and Western blot. Results：Cell prolifer-ation was inhibited inordinately after treatment of As2 S2 with 24,48 and 72h. The IC50 was（17. 64 ± 2. 11）μmol/ L, （8. 57 ± 1. 03）μmol/ L and（5. 82 ± 0. 71）μmol/ L,respectively. Flow cytometry results showed the apoptosis ratio was 4. 43 ± 0. 12,6. 50 ± 0. 09 and 8. 63 ± 0. 36 times more than normal control. qRT - PCR data showed PML -RARα mRNA was 1. 47 ± 0. 09,2. 86 ± 0. 82 and 7. 46 ± 1. 09 times more than normal control,meanwhile,PML -RARα protein was 1. 36 ± 0. 16,1. 85 ± 0. 33 and 3. 99 ± 0. 63 times more than normal control. Conclusion：As2 S2 can significantly inhibit NB4 - R2 cell proliferation and promote apoptosis which was closely related to PML - RARαfusion gene and fusion protein degradation.

关 键 词：二硫化二砷 NB4 - R2 增殖 凋亡 急性早幼粒细胞白血病 

分 类 号：R73[医药卫生—肿瘤]