第三代新维甲类化合物R9158对人急性早幼粒白血病NB_4细胞的分化诱导作用  

Induction Differentiation by a New Third Generation Retinoid R9158 on Human Acute Promyelocytic Leukemia Cell Line,NB_4

作　　者：何小庆[1] 韩锐[1] 

机构地区：[1]中国医学科学院中国协和医科大学药物研究所,北京100050

出　　处：《中国医学科学院学报》1998年第6期459-465,共7页Acta Academiae Medicinae Sinicae

摘　　要：目的　 为了研究本所合成的第三代新维甲类化合物 3′,5′,二叔丁基 - 4′-甲氧基 - 4 -羧基查尔酮酸 ( R91 5 8)对 NB4细胞的分化诱导作用。方法　 从形态、功能及染色体核型等方面观察 R91 5 8对 NB4细胞的影响。结果　 发现 R91 5 8与全反式维甲酸( RA)相似 ,可明显抑制 NB4细胞的生长及克隆形成 ,且在相同浓度下 R91 5 8的作用强于 RA。用 1 0 - 6mol/ L R91 5 8处理 NB4细胞 ,发现随作用时间的延长 NBT还原能力也明显增强 ,处理 6 d时 NBT阳性率为 97.5 %。用 R91 5 8与 RA处理 NB4细胞 ,NBT还原的 ED50 分别为 3.9× 1 0 - 9及 2 .8× 1 0 - 9mol/ L。形态学检查表明 ,用 1 0 - 6mol/ LR91 5 8及 RA诱导 2 d,可使细胞缩小 ;处理 6 d,细胞向成熟方向分化 ,但大多数细胞处于中幼及晚幼粒细胞阶段。染色体核型分析表明 ,NB4细胞具有亚四倍体型染色体核型 ,用 R91 5 8处理可使其非整倍体染色体数目下降。从对照的 80 .85± 7.5降至72 .96± 6 .9( P<0 .0 1 )。G带显示 ,用 1 0 - 6mol/ L R91 5 8及 RA处理 NB4细胞 6 d,其典型的 t( 1 5 ;1 7)易位未见消失。结论　 R91 5 8对 NB4细胞具有显著的分化诱导作用。Objective In order to investigate the differentiation of 3′,5′- ditertiary- butiary- 4′- methoxy- carboxyl chalcone( R91 5 8) on the acute promyelocytic leukemia NB4cells.Methods By inditifying the function,morphology and karyotype of NB4cells induced by R91 5 8.Re- sults Our results showed that R91 5 8or all- trans retinoic acid( RA) significantly inhibited the growth and colony formation of acute promyelocytic leukemia NB4cells,while NBT- re- duction( a functional differentiation marker of granulocytic) was dramatically increased when the cells were exposed to R91 5 8at 1 0 - 9～ 1 0 - 6 mol/L ,and the NBT positive cells reached about97.5 % at1 0 - 6mol/L after6 days expouse.The ED50 of NBT- reduction was achieved at concentration of3.9× 1 0 - 9mol/L and2 .8× 1 0 - 9mol/L for R91 5 8and RA,respectively. Morphologically,most of the cells induced by R91 5 8and RA at1 0 - 6mol/L were in the mye- locytic or metamyelocytic stage and a few cells were in the banded or segmented stage.Cyto- genetic analysis revealed that the karyotype of NB4cells was subtetraploid and the chromo- some numbers were in the range of71～ 99,when NB4cells were treated with R91 5 8or RA for3～ 6 days,the abnormal polyploid chormosome numbers decreased to72 .9± 6 .9( P< 0 .0 1 ) or6 8.5± 7.0 ( P<0 .0 1 ) ,but the t( 1 5 ;1 7) translation did not disappear.Conclusions R91 5 8has significant effects on the differentiation of NB4cells.

关 键 词：白血病 APL 药物疗法 维甲类化合物 细胞分化 

分 类 号：R733.710.5[医药卫生—肿瘤]