PARP抑制剂olaparib对急性髓系白血病细胞HL-60抑制作用研究

doi:10.11904/j.issn.1002-3070.2019.06.001

实用肿瘤学杂志 ›› 2019, Vol. 33 ›› Issue (6): 481-485.doi: 10.11904/j.issn.1002-3070.2019.06.001

• 基础研究 • 下一篇

PARP抑制剂olaparib对急性髓系白血病细胞HL-60抑制作用研究

朱志超¹, 白煜¹, 卢绪章², 孙, 晓¹, 何流漾¹, 戚春建¹

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

收稿日期:2019-07-24 修回日期:2019-09-12 发布日期:2019-12-28
通讯作者: 戚春建,E-mail:qichunjian@njmu.edu.cn
作者简介:朱志超,女,(1984-),硕士,助理研究员,从事白血病方面的研究。
基金资助:
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)

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

ZHU Zhichao¹, BAI Yu¹, LU Xuzhang², SUN Xiao¹, HE Liuyang¹, QI Chunjian¹

1.The Laboratory Center,The Second People′s Hospital of Changzhou,Affiliated Hospital of Nanjing Medical University,Changzhou 213000,China;
2.Department of Hematology,The Second People′s Hospital of Changzhou

Received:2019-07-24 Revised:2019-09-12 Published:2019-12-28

摘要/Abstract

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、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。

关键词: Olaparib, PARP抑制剂, HL-60细胞, 急性髓系白血病

Abstract: 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.

Key words: Olaparib, PARP inhibitor, HL-60 cells, Acute myeloid leukemia

中图分类号:

R733.7

朱志超, 白煜, 卢绪章, 孙, 晓, 何流漾, 戚春建. PARP抑制剂olaparib对急性髓系白血病细胞HL-60抑制作用研究[J]. 实用肿瘤学杂志, 2019, 33(6): 481-485.

ZHU Zhichao, BAI Yu, LU Xuzhang, SUN Xiao, HE Liuyang, QI Chunjian. Inhibitory effect of PARP inhibitor olaparib on acute myeloid leukemia HL-60 cells[J]. Journal of Practical Oncology, 2019, 33(6): 481-485.

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http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2019/V33/I6/481

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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

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