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目的:发掘维甲1号、维甲2号、维甲3号和维甲4号(与全反式维甲酸结构不同的新维甲类化合物)应用价值。方法:在体外研究其对人急性早幼粒细胞白血病(APL)细胞株NB4和原代APL细胞诱导分化和克隆增殖的抑制及其对正常造血细胞的促增殖作用。结果:细胞形态学、NBT反应、细胞周期动力学和CFU-L克隆形成抑制率等多参数研究表明,新维甲类化合物具有诱导NB4细胞株和原代APL细胞分化成熟及抑制CFU-L克隆生长的作用,作用强度与结构有关,维甲2号活性较强,明显高于全反式维甲酸及其它新维甲类化合物(P<0.01)。半固体造血祖细胞集落培养研究表明,新维甲类化合物能促进CFU-GM,BFU-E和CFU-Meg增殖。结论:研制的新维甲类化合物对APL细胞具有诱导分化并对其克隆生长有抑制作用,且能促进正常造血,其中以维甲2号分化作用为突出,进一步研究开发它的临床应用有一定的价值。
OBJECTIVE: To explore the application value of Vita-1, Vita-2, Viga-3, and Viga-4 (new retinoids with different structure of all-trans retinoids). METHODS: In vitro studies were conducted to investigate the inhibition of differentiation and clonal proliferation of human acute promyelocytic leukemia (APL) cell line NB4 and primary APL cells and their pro-proliferative effects on normal hematopoietic cells. RESULTS: Cellular morphology, NBT response, cell cycle kinetics, and inhibition rate of CFU-L colony formation and other multi-parameter studies showed that neuravitrin compounds induced differentiation and maturation of NB4 cell lines and primary APL cells and inhibited CFU-L cloning The effect of growth and strength of action were related to structure. The activity of Weijia No. 2 was stronger than that of all-trans retinoic acid and other retinoids (P<0.01). Colonic cultures of semi-solid hematopoietic progenitors have shown that neovitamins can promote the proliferation of CFU-GM, BFU-E and CFU-Meg. Conclusion: The developed new retinoids have the ability to induce differentiation of APL cells and inhibit the growth of APL cells, and can promote normal hematopoiesis. Among them, the differentiation effect of Vita-2 is prominent, and the clinical application of further research and development is certain. the value of.