PARP抑制剂olaparib对急性髓系白血病细胞HL-60抑制作用研究  

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

作　　者：朱志超[1] 白煜[1] 卢绪章[2] 孙晓[1] 何流漾[1] 戚春建[1] ZHU Zhichao;BAI Yu;LU Xuzhang;SUN Xiao;HE Liuyang;QI Chunjian(The Laboratory Center,The Second People′s Hospital of Changzhou,Affiliated Hospital of Nanjing Medical University,Changzhou 213000,China;Department of Hematology,The Second People′s Hospital of Changzhou)

机构地区：[1]南京医科大学附属常州市第二人民医院中心实验室,常州213000 [2]南京医科大学附属常州市第二人民医院血液科

出　　处：《实用肿瘤学杂志》2019年第6期481-485,共5页Practical Oncology Journal

基　　金：国家自然科学基金面上项目(编号:81672799);常州市卫生计生委青年人才科技项目(编号:QN201821);南京医科大学科技发展基金面上项目(编号:2017NJMU044)

摘　　要：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、10μmol/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、10μmol/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。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 10μmol/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 10μmol/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.

关 键 词：OLAPARIB PARP抑制剂 HL-60细胞 急性髓系白血病 

分 类 号：R733.7[医药卫生—肿瘤]