2-DG增强TRAIL诱导白血病细胞HL-60凋亡的作用  

2-DG Enhances TRAIL-induced Apoptosis of Leukemia HL-60 Cells

作　　者：赵素容[1] 段海峰[2] 张配[1] 刘浩[1] 蒋琛琛[1] 蒋志文[1] 

机构地区：[1]蚌埠医学院药学系,安徽省生化药物工程技术研究中心,安徽蚌埠233030 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《中国实验血液学杂志》2013年第2期351-355,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金项目(编号81000992;81072207);安徽省高校省级自然科学研究项目(编号KJ2012A202);安徽省高校省级优秀青年人才基金(编号2010SQRL122)

摘　　要：本研究旨在探讨2-脱氧葡萄糖(2-DG)增强HL-60细胞对肿瘤坏死因子相关凋亡诱导配体(TRAIL)敏感性的作用及其可能机制。采用MTT法检测不同浓度2-DG、TRAIL对HL-60细胞增殖的影响。选择低于半数抑制浓度(IC50)的10 mmol/L的2-DG和100 ng/ml的TRAIL单独或联合处理细胞,用PI单染流式细胞术检测细胞凋亡,Western blot检测RIP1、GRP78、PARP蛋白的表达,试剂盒检测caspase-3的活性变化。结果表明,2-DG(10mmol/L)与TRAIL(100 ng/ml)联合作用于HL-60细胞48 h的凋亡率为(45.1±4.3)%,较单用2-DG、TRAIL的凋亡率明显提高(P<0.01),同时二者联合应用能增强GRP78蛋白的表达及caspase-3的活性,下调RIP1蛋白的表达。结论:2-DG能增强TRAIL诱导HL-60细胞的凋亡的敏感性,其机制可能是通过引起过度的内质网应激反应、下调RIP1蛋白的表达以及增加caspase-3的活性。This study was purposed to investigate the effects of 2-deoxy-D-glucose （2-DG） on sensitizing HL-60 cells to tumor necrosis factor-related apoptosis-inducing ligand （TRAIL）-induced apoptosis and its possible mechanism. The proliferative inhibition of HL-60 cells treated with different concentrations of 2-DG and TRAIL was measured by MTT assay. The cells were treated with 2-DG, TRAIL, and 2-DG combined with TRAIL at the concentration 〈 IC50 value, i.e. 10 mmol/L for 2-DG and 100 ng/ml for TRAIL. Apoptosis was analyzed by flow cytometry with PI staining; the expression of RIP1, GRP78, and PARP was analyzed by Western blot; the activity of caspase-3 was detected by special detection kit. The results showed that the combined treatment of HL-60 cells for 48 h induced an apoptotic rate of （45.1 ± 4.3 ） %, which was significantly higher than that of treated with 2-DG or TRAIL alone; at the same time, the combined treatment potentiated the expression of GRP78 and caspase-3 activity, and down-regulated the expression of RIP1. It is concluded that 2-DG can sensitize HL-60 cells to TRAIL-induced apoptosis, which may be correlated with excessive endoplasmic reticulum stress response, down-regulation of RIP1, and increase of caspase-3 activity.

关 键 词：白血病 2-脱氧葡萄糖 肿瘤坏死因子相关凋亡诱导配体 细胞凋亡 

分 类 号：R733.71[医药卫生—肿瘤] R979.1[医药卫生—临床医学]