新型维甲酸衍生物ATPA对白血病细胞株K562增殖及分化的影响  

Effects of a new retinoic acid derivative ATPA on the proliferation and differentiation of leukemia cell line K562

作　　者：洪凡青[1] 陈飞虎[1] 王璐[1] 陈慧慧[1] 吴菲[1] 吴繁荣[1] 汪渊[2] 

机构地区：[1]安徽医科大学药学院,合肥230032 [2]安徽医科大学分子生物学实验室,生物化学教研室,安徽省省部共建教育部重要遗传病基因资源利用重点实验室,合肥230032

出　　处：《肿瘤》2011年第1期28-33,共6页Tumor

摘　　要：目的:本研究探讨新型维甲酸衍生物4-氨基-2-三氟甲基苯基依曲替酸酯(4-amino-2-trifluoromethyl-phenyl acitretinate,ATPA)对白血病K562细胞体外增殖和分化的作用。方法:用不同浓度的ATPA作用白血病K562细胞后,在体外通过MTT法检测和绘制细胞生长曲线来分析细胞增殖;瑞特染色法观察细胞形态学改变;氯化硝基四氮唑蓝(nitroblue tetrazolium chloride,NBT)还原实验分析细胞的分化指标;采用FCM法检测细胞表面分化抗原及细胞周期的变化。结果:ATPA呈浓度依赖性抑制K562细胞增殖,明显的抑制作用从药物作用48h后开始出现,在72h后作用更明显。倒置显微镜下观察发现ATPA作用后K562细胞形态趋向成熟,NBT阳性细胞率增加;G0/G1期细胞表达量增加,S期细胞表达量减少,呈G0/G1期阻滞;细胞表面分化抗原CD71表达减少。结论:ATPA对白血病K562细胞具有抑制增殖和一定的诱导分化作用。Objective： To explore the effects of 4-amino-2-trifluoromethyl-phenyl acitretinate （ATPA） on the proliferation and differentiation of K562 leukemia cells in vitro. Methods： After K562 leukemia cells were treated with ATPA at different concentrations, cell proliferation was assessed by MTT and cell growth curve. Morphologic changes of cells were observed under an inverted microscope （oil- immersion lens） after Wright＇s staining. Nitroblue tetrazolium （NBT） reduction test was used to analyze cell differentiation indices. The cell cycle and the expression of the specific cell surface maturation marker CD71 were analyzed by flow cytometry （FCM）. Results： The growth of K562 cells treated with ATPA was inhibited in a dose-dependent manner. The distinct inhibitory effect appeared after treatment with ATPA for 48 h, but the effect was more significant after 72 h. Morphology of K562 cells treated with ATPA was observed to be mature under an inverted microscope. NBT reduction test indicated that ATPA could increase the percentage of NBT-positive cells. ATPA increased the proportion of cells in the G0/G1 phase and decreased the proportion in the S phase, so that cell cycle progression was blocked in the Go/ G1 phase. The expression of the specific cell surface maturation marker CD71 was decreased. Conclusion： ATPA can inhibit the proliferation of leukemia K562 cells and induce their differentiation in some degree.

关 键 词：白血病 实验性 阿维A 细胞增殖 细胞分化 K562细胞 维甲酸衍生物 ATPA 

分 类 号：R733.7[医药卫生—肿瘤] R73-34[医药卫生—临床医学]