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.