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三氧化二砷对急性早幼粒细胞性白血病细胞株的双重效应研究 被引量:48

Double effects of arsenic trioxide (As 2O 3) on acute promyelocytic leukemic cell line
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摘要 观察不同浓度的三氧化二砷(As2O3)对急性早幼粒细胞性白血病(APL)细胞株NB4细胞的影响。方法不同浓度的三氧化二砷(0.1~2μmol/L)与APL细胞株NB4细胞共同孵育一定时间后,观察NB4细胞的存活,细胞形态学,免疫表型(CD11b,CD33),细胞DNA含量分布及PML/PML-RARα蛋白在细胞内定位的改变。结果经1~2μmol/L氧化砷处理的NB4细胞呈现凋亡的特征性改变。在细胞形态学上表现为胞膜完整,染色质固缩及核碎裂。流式细胞仪分析显示与三氧化二砷作用浓度及时间相关的亚G1期细胞。经0.1~0.25μmol/L三氧化二砷处理10天的NB4细胞呈现某些与分化相关的形态学改变和分化相关抗原(CD11b和CD33)的调变,而0.1~2μmol/L的三氧化二砷均能快速调变和减少PML/PML-RARα蛋白的表达。结论氧化砷对NB4细胞具有诱导凋亡和不完全分化双重作用,并能快速调变及降解PML/PML-RARα蛋白的表达。 Objective To investigate the effects of a wide range of concentrations of As 2O 3 on NB 4 cells. Methods Cell morphology, cell DNA content distribution, CD11b and CD33 antigens and nitroblue tetrazolium (NBT) reductions were evaluated in an APL cell line NB 4 cells with or without As 2O 3 treatment. In addition, immunofluorescent analysis for APL marker molecule PML RAR α was also performed. Results 1~2 μmol/L of As 2O 3 treated NB 4 cells presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation. Sub G1 cells ,whose percentage presents concentration and time dependency, were observed by flow cytometer. Otherwise, NB 4 cells with the treatment of As 2O 3 at 0.1~0.25 μmol/L for a long time (10 days) have differentiation related morphology, and their differentiation antigens CD11b and CD33 were also modulated to some extent. In addition, 0.1~2 μmol/L of As 2O 3 could rapidly and effectively modulate and degradate PML/PML RAR α proteins. Conclusion As 2O 3 had double effects (induction of apoptosis and imcomplete differentiation) on NB 4 cells, which could associate with rapid modulation and degradation of PML/PML RARα proteins.
出处 《中华医学杂志》 CAS CSCD 北大核心 1997年第7期509-512,共4页 National Medical Journal of China
基金 国家自然科学基金 卫生部优秀青年基金 上海科技启明星计划 上海血液学研究所胡应洲基金
关键词 氧化砷 白血病 早幼粒细胞性 急性 细胞分化 Arsenic trioxide Leukemia, myelocytic, acute Cell differentiation
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参考文献7

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