维甲类化合物R8607对人急性早幼粒白血病NB4细胞的分化及其作用机理

目的　研究维甲类化合物R8607对人急性早幼粒白血病NB4细胞的分化诱导作用及其作用机理。方法　采用NBT还原能力和细胞形态的方法观察R8607对NB4细胞功能和形态的分化作用，采用竞争性结合的方法测定R8607和维甲酸受体的结合能力并用流式细胞术观察其对细胞周期移行的影响。结果　R8607有抑制NB4细胞的生长并能使细胞的功能和形态发生分化的作用； 对维甲酸受体的3个亚型α，β，γ均有结合作用并将NB4细胞周期移行阻断在G₁期。结论　R8607通过维甲酸受体的调节通路将NB4细胞阻断在G1期并诱导细胞发生功能和形态的分化。

DIFFERENTIATION EFFECT OF A RETINOIC ACID DERIVATIVE R8607 ON HUMAN ACUTE PREMYELOCYTIC LEUKEMIA NB4 CELL LINE AND ITS MECHANISM

AIM　To study the differentiation effect of a retinoic acid derivative R8607 on human acute premyelocytic leukemia NB4 cell line and its mechanism. METHODS　NBT reduction and morphology observation were employed for the differentiation investigation; the binding ability assay of R8607 to retinoic acid receptors RARα, RARβ and RARγ were performed; and the effect of this compound on cell cycle were followed by flow cytometric assay. RESULTS　The NB4 cell proliferation was shown to be inhibited for 85% by R8607 after 6 days exposure at 10^-6　mol.L^-1.　Accompanying the NBT reduction positive cells increased from 5% to 100%. Morphology changes were also observed with 25% cells as the premyelocytic cells, 71% as the myelocytic cells, 2% as the metamyelocytic cells and the other 2% as the Banded and segmented cells. R8607 was found to bind to all the three retinoic acid subtype receptors with IC₅₀ 70　nmo.L^-1， 24　nmol.L^-1 and 40 mol.L^-1 for RARα, RARβ and RARγ, respectively. The effect on cell cycle showed that it could accumulate the NB4 cells in G1 phase up to 69.12% after 96 h incubation. CONCLUSION　By binding to RAR receptors, R8607 was shown to accumulate the NB4 cells in G1 phase, and induce functional and morphological differentiation of the cell line.