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目的探讨地西他滨(DCA)和丙戊酸钠(VPA)联用对白血病细胞株HL-60促凋亡和分化诱导的协同作用。方法白血病细胞株HL-60分别与以下药物终浓度组作用48 h:对照组,DCA单药A组(1.0μmol·L~(-1)),DCA单药B组(4.0μmol·L~(-1)),VPA单药组(2.0 mmol·L~(-1)),联合用药A组(IDCA 1.0μmol·L~(-1)+VPA 2.0 mmol·L~(-1)),联合用药B组(DCA 4.0μmol·L~(-1)+VPA2.0 mmol·L~(-1))。应用Annexin V-FTTC/PI标记法检测早期凋亡率,流式细胞术检测CD34、CD117平均荧光强度(MFI)以及CD11b、CD14表达率。结果联合用药A、B组的凋亡率高于其各自的单药组,差异具有高度统计学意义(P<0.01);联合用药A、B组的CD117和CD34 MFI低于其各自的单药组,差异具有高度统计学意义(P<0.01);联合用药A组的CD11b和CD14表达率以及联合用药B组的CD11b表达率均低于其各自的单药组,差异具有高度统计学意义(P<0.01)。结论白血病细胞株HL-60中VPA能显著增强DCA的促凋亡分化作用。
Objective To investigate the synergistic effect of decitabine (DCA) and sodium valproate (VPA) on the induction of apoptosis and differentiation of leukemia cell line HL-60. Methods Leukemia cell line HL-60 was treated with final concentration of 48 h for control group, DCA monotherapy group (1.0μmol·L -1), DCA monotherapy group B (4.0μmol·L -1 (2.0 mmol·L -1), combination group A (IDCA 1.0 μmol·L -1 + VPA 2.0 mmol·L -1), combined with Group B (DCA 4.0 μmol·L -1 + VPA 2.0 mmol·L -1). The rate of early apoptosis was detected by Annexin V-FTTC / PI. The average fluorescence intensity (MFI) of CD34 and CD117 and the expression of CD11b and CD14 were detected by flow cytometry. Results The apoptotic rates of group A and group B were higher than those of group A and group B respectively (P <0.01). The MFIs of CD117 and CD34 of group A and group B were lower than those of group A and group B (P <0.01). The expression rates of CD11b and CD14 in combination group A and the expression of CD11b in combination group B were lower than those in single drug group (P <0.01), the difference was highly statistically significant (P < P <0.01). Conclusion VPA in leukemia cell line HL-60 can significantly enhance the pro-apoptotic differentiation of DCA.