氧化砷诱导维甲酸耐药早幼粒细胞白血病细胞(MR-2)凋亡的体外研究

In vitro study on arsenic trioxideinduced apoptosis of retinoic acid resistant acute promyelocytic leukemia cell line(MR-2)

目的：深入了解氧化砷（Ａｓ２Ｏ３）治疗急性早幼粒细胞白血病（ＡＰＬ）的机制。方法：以对全反式维甲酸耐药的ＡＰＬ细胞株ＭＲ２为模型，用细胞生长、活力测定、形态学观察和流式细胞仪分析、四氮唑蓝还原反应及免疫荧光等指标观察Ａｓ２Ｏ３治疗ＡＰＬ的效应途径。结果：１．０μｍｏｌ／ＬＡｓ２Ｏ３可诱导ＭＲ２细胞凋亡，并能降解ＡＰＬ特异蛋白ＰＭＬＲＡＲα融合蛋白。结论：Ａｓ２Ｏ３治疗ＡＰＬ的效应途径可能不同于ＡＴＲＡ。

Objective:To study the possible mechanisms of arsenic trioxide (As_2O_3)in the treatment of acute promyelocytic leukemia (APL). Methods:Retinoic acid resistant APL cell line MR-2 was used as in vitro model. The effect of As_2O_3 on MR-2 cell line was observed by cell viability,cell growth,cell morphology,flow cytometry assay,NBT reduction test and immunofluorescence analysis. Results:1.0μmol/L of As_2O_3 could induce apoptosis of MR-2 cells and it correlated with the degradation of PML-RARα fusion protein. Conclusions: The therapeutic effect of As_2O_3 for APL possibly differs from that of ATRA, however, PML-RARα fusion protein may be the target of both the therapy.