氟伐他汀对人早幼粒细胞白血病HL-60细胞的诱导分化作用

目的:探讨氟伐他汀对人早幼粒细胞白血病HL-60细胞的分化诱导作用，为人类早幼粒细胞白血病的治疗提供理论依据。方法：体外培养HL-60细胞用20 μmol·L^-1氟伐他汀处理，观察细胞分化的形态学改变。20 μmol·L^-1氟伐他汀处理HL-60细胞72 h后测定硝基四氮唑蓝（NBT）还原能力，5 d后进行非特异性酯酶染色，计算分化细胞百分率。结果:经氟伐他汀处理的HL-60细胞，胞体较小，核/质比例降低，核呈扭曲折叠状或分叶状，细胞质内出现特异性颗粒及空泡样改变，部分细胞已分化为较成熟的细胞。用氟伐他汀处理的HL-60细胞NBT还原能力(A值)较对照组显著升高（P<0.01），与阳性对照组全反式维甲酸（ATRA，10 μmol·L^-1）的作用大致相当。经20 μmol·L^-1氟伐他汀处理5 d的HL-60细胞，非特异性酯酶染色阳性细胞的百分比明显多于对照组(P<0.01)，在作用液中加入氟化钠未能抑制该种阳性反应。结论:氟伐他汀可使HL-60细胞分化为较成熟的细胞，提示氟伐他汀可能成为治疗急性早幼粒细胞白血病的药物。

Effect of fluvastatin on induction and differentiation of human promyelocytic leukemia HL-60 cells

Objective To observe the effect of fluvastatin(Flu) on differentiation and induction of human promyelocytic leukemia HL-60 cells and provide the theoretical foundation for treatment of human promyelocytic leukemia.Methods The cultured HL-60 cells were treated with 20 μmol·L-1 Flu,the morphological changes of the cell differentiation were examined.The NBT reduction capability was detected in HL-60 cells treated with Flu for 72 h.After HL-60 cells were treated with 20 μmol·L-1 Flu for 5 d,they were stained with non-specific esterase and the percentage of differentiation cells was analyzed.Results The HL-60 cells treated with Flu showed smaller cell body,reducing proportion of nucleus to cytoplasm,the nucleus tortuosity,fold or sublobe.There were specific granules and vacuoles in cytoplasm,displaying that some cells had differentiated to relative mature cells.As compared with control group,the NBT reduction capability in HL-60 cells treated with Flu for 72 h was significantly higher than that in control cells(P<0.01),which was similar to that of ATRA(10 μmol·L-1).After HL-60 cells were treated with 20 μmol·L-1 Flu for 5 d,the percentages of positive cells were markedly higher than those in untreated HL-60 cells,and the positive reaction was not inhibited by NaF.Conclusion Flu treatment can result in differentiation of HL-60 cells to relative mature cells,it indicates that Flu may be used as a drug for treatment of human promyelocytic leukemia.