The Effectiveness Of Valproate Acid And All-trans Retinoic Acid Treat NOD/SCID Mouse Of Acute Promyelocytic Leukemia

ObjectiveThe aim was to observe the effect that the histone deacetylaseinhibitor valproic acid (VPA) impact on human acute promyelocyticleukemia (APL) cell line NB-4cell proliferation and apoptosis in vitro.An animal model of human acute promyelocytic leukemia in NOD/SCID mouse was established in NB-4cells. Use all-trans retinoic acid(ATRA) alone or combine valproic acid to treat these models and analyzeinvestigate the effectiveness.MethodsThe NB-4cells were cultured at37℃in RPM1640medium whichcontaining10%fetal bovine serum in5%CO2incubator. The effects ofdifferent concentrations (0mmol/L,1mmol/L,2mmol/L,4mmol/L)VPA for NB-4cell proliferation and apoptosis were observed in vitro.Take logarithmic phase cells to established NOD/SCID mouse model ofhuman acute promyelocytic leukemia, successful modeling method micewere randomly divided into three groups, namely, the ATRA group, VPA+ATRA group and control group. Generally observed three groups of mice, WBC and leukemia cell count, record survival time, Western blotdetection of peripheral blood mononuclear cells of mouse histone H3, H4acetylation of expression. SPSS16.0analysis of these data.Results1．After different concentrations of VPA impact on NB-4cells, withthe increase in drug concentration and prolonged duration of action, thegradual growth of the cells was inhibited in a time-a dose-dependentmanner.2．Different concentrations of VPA were acting on the NB-4,apoptotic cells increased, compare to the control group (P <0.05), flowcytometry shows G0/G1phase cells display increased compared with thecontrol group.3．Three weeks after intraperitoneal injection of NB-4cells27mouse leukemia cells in peripheral blood smear shows. ATRA group,VPA+ATRA leukemic cell counts in peripheral blood of mice comparedto reduce the incidence of early and peripheral blood mononuclear cellsexpressing histone acetylation higher than the control group (P <0.05).4．The survival time of mice in group VPA+ATRA are longer thangroup ATRA and control groups (P <0.05).ConclusionVPA can inhibit NB-4cell proliferation and induce apoptosis; VPAcombined ATRA are better than ATRA to treat APL.