三氧化二砷及全反式维甲酸对白血病NB4细胞PML/RARA融合基因的影响

目的探讨在NB4细胞增殖过程中PML/RARA融合基因表达的情况,并用三氧化二砷(As2O3)和/或全反式维甲酸(All trans retinoic acid,ATRA)干扰后观察目的基因的变化。方法用As2O3(1×106 mol/L)或/和ATRA(1×106 mol/L)干扰体外培养成熟的NB4细胞,后用real/Time PCR检测PML/RARA融合基因的相对表达量。结果ATRA及As2O3均使PML/RARA融合基因表达抑制,但双药联用无明显协同作用(P<0.05)。As2O3对PML/RARA融合基因表达抑制较同剂量ATRA强。结论 ATRA及As2O3均能下调PML/RARA融合基因。As2O3对PML/RARA融合基因的下调作用及对NB4细胞的增殖抑制均比同剂量的ATRA强。双药联用与单药干预,无叠加效应。

The effect of As2O3 and ATRA on the PML/RARA gene in Myeloid Leukemia Cells NB4

Objective To detect the expression of PML/RARA gene （ PML/RARa target gene） in myeloid leuke- mia cells NB4 influnced by As2O3 and/or ATRA. Methods NB4 cell line was cultured by As2O3 （1×10^6 mol/1 ） and/or ATRA （1×10^6mol/1 ） for 3 days. PML/RARA gene was deteeted by Real/Time PCR. Results Gene PML/RARA ex- pressed regularly, which was higher on the 2nd day and lower on the 3nd day. By adding 10/6mol/1 As203 and/or AT- RA （1×10^6 mol/1 ）, the expression of PML/RARA gene was down--regulated than the normal group, specially at the 2nd day, while either As203 （1×10^6mol/1 ） or ATRA （1×10^6mol/1 ）ean attenuate NB4 cells to mature, but no obvious cooperation of the two drugs to PML/RARA gene. Conclusion 1×10^6 mol/1 As2O3 or ATRA leads to the expression of PML/RARA gene decreased as they attenuate NB4 cells to mature, suggesting their treatment effects of APL eel1 through PML/RARA gene site. And the role of As2O3 is severer than which of ATRA on the same dose either on the gene or the NB4 cells t maturation.. The down-regulated effect of the two drugs together on gene PML/RARA is similar to which of As2O3.