CAJ | 학술논문

目的探讨RARβ特异性激动剂/RARα特异性拮抗剂（RARβ+/RARα-）BMS453与RXR 特异性激动剂（RXR+）BMS649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 BMS453+BMS649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0，1，3，12，24，48?h，RARα基因表达在1?h开始上调，RARβ基因表达在3?h开始上调，RXRα基因表达在3?h开始上调；与全反式维甲酸（ATRA）相比差异无显著性。BMS453和BMS649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AF-2活性调节NB4细胞的生长和分化过程。
목적탐토RARβ특이성격동제/RARα특이성길항제（RARβ+/RARα-）BMS453여RXR 특이성격동제（RXR+）BMS649대NB4세포증식、분화작용급분자궤제。방법응용세포계수법、세포형태학관찰、초기사담서람(NBT)환원시험、간접면역형광、류식세포의、RT-PCR등방법대약물처리불동시간적NB4세포진행연구。결과 BMS453+BMS649대NB4세포적생장구유제량의뢰성억제작용；명현유도NB4세포향립계성숙방향분화；약물작용NB4세포0，1，3，12，24，48?h，RARα기인표체재1?h개시상조，RARβ기인표체재3?h개시상조，RXRα기인표체재3?h개시상조；여전반식유갑산（ATRA）상비차이무현저성。BMS453화BMS649단용대NB4세포계무차작용。결론 RARβ+/RARα-저일유갑류수체아형화합물여RXR격동제연합응용억제NB4세포생장병유도NB4세포분화성숙，이자구유협동작용，기작용궤제가능통과RXRα적AF-2활성조절NB4세포적생장화분화과정。
Objective　To investigate the effects of RARβ selective agonist and RARα antagonist (RARβ+/RARα-) BMS453 in combination with RXR selective agonist (RXR+) BMS649 on the proliferation and differentiation of NB4 cells ,and illustrate the mechanism. Methods　The proliferation and differentiation of NB4 cells were detected by cell count, morphological observation, NBT reduction assay, immunofluorescence analysis, flow cytometry and RT-PCR. Results　BMS453 in combination with BMS649 could significantly inhibited the growth of NB4 cell in the manner 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 significant difference. In contrast, BMS453 or BMS649 alone was ineffective on NB4 cells. Conclusion　BMS453(RARβ+/RARα-) in combination with BMS649 (RXR+) significantly and synergistically inhibit proliferation of NB4 cells and induce them into granulocytic differentiation, the mechanism of which may be mediated by the AF-2 activity of RXR.