丹参酮ⅡA诱导NB4细胞分化与PML-RARα融合蛋白的关系  

Relationship between the PML-RARα protein and the differentiation of NB4 cells induced by TanⅡA

作　　者：郭庆寅[1] 伍学强[2] 刘玉峰[1] 

机构地区：[1]郑州大学第一附属医院儿科,河南郑州450000 [2]北京航天总医院血液肿瘤研究所,北京100076

出　　处：《中国癌症杂志》2012年第1期15-20,共6页China Oncology

摘　　要：背景与目的:目前研究证实丹参酮ⅡA(TanⅡA)对白血病细胞具有抑制增殖、诱导分化和促凋亡的作用,但其具体作用机制尚不明确。本实验旨在研究TanⅡA与全反式维甲酸(all-tram retinoid,ATRA)及三氧化二砷(As2O3)诱导NB4细胞分化在细胞形态学、免疫表型和对PML-RARα融合基因及其蛋白影响的比较。方法:采用免疫荧光法观察NB4细胞内PML蛋白,Western blot检测PML-RARα融合蛋白,实时定量PCR方法检测PML-RARαmRNA;同时计算细胞生长抑制率,观察细胞形态学、免疫表型的变化。结果:TanⅡA能抑制NB4细胞生长,诱导分化,使NB4细胞PML蛋白异常分布重新定位、NBs结构恢复、PML-RARα融合蛋白降解。结论:降解PML-RARα融合蛋白可能是TanⅡA诱导NB4细胞分化的机制。Background and purpose：Recently,it was reported that TanⅡA could inhibit proliferation,induce differentiation and apoptosis of human leukemia cells,but the mechanism in the treatment of acute promyelocytic leukemia of TanⅡA is still poorly understood.Our study was to investigate the relationship between the PML-RARα fused protein and the differentiation of NB4 cells induced by TanⅡA,and to compare the differentiation with all-tram retinoid（ATRA） and arsenic trioxide（As2O3）.Methods：The PML-RARα fused protein in NB4 cells was measured by Western blot,PML protein was observed under fluorescence microscopy,PML-RARα mRNA was assayed by Real-time Q-PCR.Results：TanⅡA could inhibit the proliferation and induce the differentiation of NB4 cells.TanⅡA could degradate PML-RARα protein in NB4 cells,relocate PML protein into its normal position in NB4 cell nuclei and restore the normal structure of nuclear bodies of NB4 cells with a dose and time-dependent relationship.Conclusion：Degradation of PML-RARα protein may be the pathogenesis of TanⅡA inducing the differentiation of NB4 cells.

关 键 词：丹参酮ⅡA NB4细胞 细胞分化 PML-RARΑ融合蛋白 

分 类 号：R733.71[医药卫生—肿瘤]