新维甲类化合物对早幼粒细胞白血病和正常造血增殖分化作用的体外研究

In vitro study on the effects of the novel retinoids on the proliferation and differentiation of normal and leukemic cells

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 evaluate the prospect for clinical use of four novel retinoid compounds (retinoid 1,retinoid 2,retinoid 3 and retinoid 4), which were different structurally from all trans retinoic acid.Methods:The effects of the four retinoids on the differentiation and clonal proliferation of NB 4 cells and fresh acute promyelocytic leukemia (APL) cells and on the proliferation of normal hematopoietic cells were studied.Cell morphological examination,nitro tetrazolium blue reduction test,cell cycle dynamics,and colony formation assay were used in the study.Results: Novel retinoids induced differentiation of NB 4 and fresh APL cells, and markedly inhibited CFU L growth of NB 4 and fresh APL cells.The activity related to their chemical structures and retinoid 2 was more active.The novel retinoids enhanced the growth of CFU GM,CFU E and CFU Meg of normal bone marrow cells.Conclusion:These novel retinoids,especially retinoid 2 ,may regulate the proliferation and differentiation of normal hematopoiesis,induce APL cell differentiation and maturation ,and are worthy of further study for clinical use.