PARP抑制剂olaparib对急性髓系白血病细胞HL-60抑制作用研究

目的 研究PARP抑制剂olaparib对人急性髓系白血病细胞株HL-60细胞的抑制作用。方法 对数生长期HL-60细胞经不同浓度(0、1.25、2.5、5、10 μmol/L)olaparib作用不同时间后,CCK-8法检测olaparib对HL-60细胞的增殖抑制作用;Annexin-V/PI双标法检测HL-60细胞凋亡水平,Western blot检测HL-60细胞内相关信号蛋白(PARP-1、Caspase-3)表达变化。结果 与对照组相比,经不同浓度(1.25、2.5、5、10 μmol/L)olaparib作用48 h后的HL-60细胞出现增殖抑制,并且随着作用时间的延长,抑制率逐渐增加;同时发现olaparib诱导HL-60细胞发生凋亡,并显示出剂量依赖效应;Western blot结果显示,olaparib处理后的HL-60细胞内PARP活性受到抑制,Caspase-3活化。结论 PARP抑制剂olaparib对HL-60细胞不仅具有增殖抑制作用,同时可通过激活Caspase-3,抑制PARP活性,诱导HL-60细胞凋亡。

Inhibitory effect of PARP inhibitor olaparib on acute myeloid leukemia HL-60 cells

Objective The inhibitory effect of the PARP inhibitor olaparib on human acute myeloid leukemia HL-60 cells was studied.Methods The HL-60 cells in logarithmic growth phase were treated with different concentrations(1.25,2.5,5 and 10 μmol/L)of olaparib for different time.The CCK-8 assay was used to detect the inhibitory effect of olaparib on HL-60 cells.The apoptotic level of HL-60 cells was detected by Annexin-V/PI double staining method,and the expression of related signal proteins(PARP-1 and caspase-3)in HL-60 cells was detected by Western blot.Results HL-60 cells were inhibited by olaparib at different concentrations(1.25,2.5,5 and 10 μmol/L)for 48 h,and the inhibition rate gradually increased with the prolongation of the action time;at the same time,the apoptotic rate was increased in HL-60 cells after olaparib treatment for 48 h,showing a dose-dependent manner;the PARP activity was inhibited and caspase-3 was activated in HL-60 cells treated with olaparib.Conclusion The PARP inhibitor olaparib not only inhibits proliferation of HL-60 cells,but it also promotes apoptosis of HL-60 cells by inhibiting PARP activity and activating caspase-3.