PP2A激活剂对HL-60细胞增殖的影响及急性髓系白血病患者体内PP2A活性变化的研究

Influence of PP2A Activator on Proliferation of HL-60 Cells and Analysis of PP2A Activity Changes in Patients with Acute Myeloid Leukemia

本研究探讨蛋白磷酸酯酶2A(protein phosphotase2A,PP2A)激活剂或抑制剂对体外HL-60细胞增殖的影响及急性髓系白血病(acute myeloid leukemia,AML)患者体内单个核细胞中PP2A的活性变化。单独使用PP2A激活剂FTY720或FTY720联合冈田酸(OA)处理HL-60细胞24小时,应用CCK8试剂盒检测细胞的增殖状况;同时选取20例初发或复发的AML患者,使用PP2A免疫沉淀磷酸酶活性检测试剂盒检测AML患者及正常对照组外周血单个核细胞中PP2A活性,使用SPSS16.0软件对数据进行分析。结果显示:FTY720组细胞增殖受到明显抑制,与对照组相比差异有显著性(p<0.05);FTY720+OA组细胞增殖受到轻微抑制,与对照组相比差异无显著性(p>0.05),与FTY720组相比差异有显著性(p<0.05)。AML患者单个核细胞PP2A的活性(453.67±102.52pmol磷酸盐)与正常人(673.29±96.32pmol磷酸盐)比较明显降低,两组之间差异有显著性(p<0.01)。结论 :PP2A的激活或抑制能影响HL-60细胞的增殖;AML患者单个核细胞中PP2A的活性有所降低。PP2A蛋白与AML的发生、发展密切相关,对AML的诊断及治疗可能有参考价值。

In order to investigate the effect of PP2A activator and PP2A inhibitor on proliferation of HL-60 cells and analyze the changes of PP2A activity in patients with acute myeloid leukemia （AML）, HL-60 cells were treated with FTY720 alone or in combination with okadaic acid （OA） for 24 hours in culture. Cell proliferation was assayed with CCK8 kit. In addition, 20 AML patients including de novo AML and relapsed AML were enrolled in this study. The activity of PP2A in the peripheral blood mononuclear cells of patients was assayed with a PP2A Immunoprecipitation Phosphatase Assay Kit, the data were analyzed by software SPSS 16.0. The results indicated that as compared with control group, the proliferation of cells in FTY720 group was obviously inhibited （p 〈0.05 ）. The proliferation of cells in FFY720 ＋ OA group was slightly inhibited as compared with the control group, there was no statistical difference （p 〉0.05）, but there was significant difference between the FTY720 ＋ OA and FTY720 groups （p 〈 0.05 ）. The activity of PP2A in AML patients （453.67 ± 102.52 pmol phosphate） was obviously lower than that in the normal controls （673. 29 ± 96.32 pmol phosphate）, there was significant difference between them（p 〈0.01 ）. It is concluded that the activation or inhibition of PP2A can affect the proliferation of HL-60 cells in vitro. Compared with healthy individuals, the activity of PP2A in AML patients is obviously lower. PP2A protein playing a key role in the occurrence and development of AML may be valuable for the diagnosis and treatment of AML.