氧化砷诱导早幼粒细胞白血病细胞凋亡的体外研究

In vitro study on arsenic trioxideinducing apoptosis in primary acute promyelocytic leukemic cells

目的：阐明氧化砷治疗急性早幼粒细胞白血病（ＡＰＬ）的机制。方法：以原代ＡＰＬ细胞为模型，将不同浓度的氧化砷作用于ＡＰＬ细胞，并对其作用机制进行研究。结果：高浓度氧化砷选择性诱导ＡＰＬ细胞凋亡，低浓度氧化砷诱导新鲜ＡＰＬ细胞部分分化。进一步研究发现，不同浓度的氧化砷均能快速调变和降解ＰＭＬ－ＲＡＲα蛋白。结论：氧化砷对ＡＰＬ细胞存在双重效应，即诱导凋亡和部分分化。

Objective:To illustrate mechanisms of arsenic trioxide(As2O3) in the treatment of acute promyelocytic leukemia(APL).Methods:CellDNA content distribution,CD11band CD33antigens and nitroblue tetrazolium (NBT) reduction were evaluated in fresh APL cells from six APL patients treated in vitro with As2O3.Results:As2O3 had double effects on the cells inducing apoptosis and inducing partial differentiation at higher and at lower drug concentrations,respectively.As2O3(0.1～2.0μmol/L) could rapidly modulate and degrade APLspecific marker molecule PMLRARα protein,which could play an important role in the effects of As2O3 on APL cells.Conclusion:As2O3 had double effects (induction of apoptosis and partial differentiation) on APL cells through the modulation and degradation of PMLRARα proteins.