摘要
本研究旨在探讨氯法拉滨诱导急性髓系白血病(AML)细胞U937自噬性死亡的机制。不同浓度氯法拉滨作用U937细胞24、48 h后,用MTT法计算细胞生长抑制率及氯法拉滨半数抑制浓度(IC50),流式细胞术检测细胞自噬率的变化;Western blot方法检测细胞自噬相关蛋白Beclin 1的表达变化。结果表明,0.01和0.15μmol/L氯法拉滨作用U937细胞48 h,增殖抑制率分别为(46.92±4.24)%和(86.10±1.16)%,IC50为0.022μmol/L,与对照组比较差异有统计学意义(P<0.05)。0.01和0.1μmol/L氯法拉滨作用U937细胞48 h,自噬率分别为(11.0033±1.4387)%和(59.4133±3.5409)%,且呈剂量依赖性增强(r=0.99);随药物浓度的增加,Beclin 1表达逐渐上调,与对照组比较差异有统计学意义(P<0.05)。结论:氯法拉滨对U937细胞有明显的增殖抑制作用,且存在剂量依赖性,其作用机制可能是通过上调Beclin 1的蛋白表达诱导U937细胞自噬性死亡。
To explore the mechanism of autophagic death of acute myelocytic leukemia cell U937 induced by clofarabine, the MTT bioassay was used to analyze the growth inhibitory effect and half inhibition concentration on U937 incubated in vitro with different concentrations of clofarabine for 24 and 48 hours, and the flow cytometry was used to detect the autophagy rate of U937. The expression of Beclin 1 in U937 treated by clofarabine for 48h was meaused by Western blot. The results indicated that when U937 cells were treated with 0.01μmol/L and 0.15 μmol/L clofarabine for48 hours,the proliferation inhibition rate was 46.92% ±4.24% and 86. 10% ± 1. 16%, and the half inhibition concentration of clofarabine was 0.022 μmol/L. With 0.01 μmol/L and 0.1μmol/L clofarabine on U937 for 48 hours, the autophagy rate was 11. 0033% ± 1. 4387% and 59.4133% ± 3. 5409% ,and increased in dose-dependent manner（ r = 0.99）. Meanwhile the Beclin 1 was upregulated along with increase of clofarabine concentration, as compared with control group, the difference was statistically significant （ P 〈 0.05 ）. It is concluded that the different concentrations of clofarabine can significantly inhibit the proliferation of U937 in dose-dependent manner, and the mechanism of autophagic cell death in U937 may be associated with the upregulation of Beclin 1 expression.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2013年第2期347-350,共4页
Journal of Experimental Hematology
