维甲类受体亚型化合物对NB4细胞增殖分化作用及分子机制研究  

Effects of selective RAR or/and RXR retinoids on the proliferation and different iation of NB4 cells and their mechanisms

作　　者：陈睿博[1] 陈芳源[1] 韩洁英[1] 缪金明[1] 邵念贤[1] 欧阳仁荣[1] 

机构地区：[1]上海血液学研究所白血病研究室

出　　处：《中华血液学杂志》2001年第5期256-259,I002,共5页Chinese Journal of Hematology

摘　　要：目的　探讨RARβ特异性激动剂 /RARα特异性拮抗剂 (RARβ +/RARα - )BMS45 3与RXR特异性激动剂 (RXR +)BMS6 49对NB4细胞增殖、分化作用及分子机制。方法　应用细胞计数法、细胞形态学观察、硝基四氮唑蓝 (NBT)还原试验、间接免疫荧光、流式细胞仪、RT PCR等方法对药物处理不同时间的NB4细胞进行研究。结果　BMS45 3+BMS6 49对NB4细胞的生长具有剂量依赖性抑制作用 ;明显诱导NB4细胞向粒系成熟方向分化 ;药物作用NB4细胞 0 ,1,3,12 ,2 4,48h ,RARα基因表达在 1h开始上调 ,RARβ基因表达在 3h开始上调 ,RXRα基因表达在 3h开始上调 ;与全反式维甲酸 (ATRA)相比差异无显著性。BMS45 3和BMS6 49单用对NB4细胞系无此作用。结论　RARβ +/RARα -这一维甲类受体亚型化合物与RXR激动剂联合应用抑制NB4细胞生长并诱导NB4细胞分化成熟 ,二者具有协同作用 ,其作用机制可能通过RXRα的AFObjective To investigate the effects of RARβ selective agonist and RARα antagonist (RAR β+/RARα-) BMS453 in combination with RXR selective agonist (RXR+) BMS649 on th e proliferation and differentiation of NB4 cells ,and illustrate the mechanism. MethodsThe proliferation and differentiation of NB4 cells were d etected by cell count, morphological observation, NBT reduction assay, immunoflu orescence analysis, flow cytometry and RT PCR. ResultsBMS453 in combin ation with BMS649 could significantly inhibited the growth of NB4 cell in the ma nner of dose and time dependence. NB4 cells treated with BMS453 and BMS649 were irreversibly committed to morphologically and functionally more differentiated granulocytic cells. When NB4 cells were treated with BMS453 and BMS649 for 0, 1 , 3, 12, 24 and 48?h, RARα,RARβ and RXRα expressions were up regulated at 1 h and 3h, respectively. As compared to ATRA, the situations had no signific ant difference. In contrast, BMS453 or BMS649 alone was ineffective on NB4 cells . ConclusionBMS453(RARβ+/RARα-) in combination with BMS649 (RX R+) significantly and synergistically inhibit proliferation of NB4 cells and ind uce them into granulocytic differentiation, the mechanism of which may be media ted by the AF 2 activity of RXR.

关 键 词：维甲类受体亚型化合物 激动剂 拮抗剂 细胞分化 急性早幼粒细胞白血病 

分 类 号：R733.7[医药卫生—肿瘤]