中国药理学通报Issue(6):763-768,769,7.DOI:10.3969/j.issn.1001-1978.2015.06.006
BMS-345541对急性粒细胞白血病细胞DNA损伤修复的影响
BMS-345541 regulates repair of DNA double-strand breaks induced by VP-16 in acute myeloid leukemia cells
摘要
Abstract
Aim To investigate the effect of BMS- 345541 on the repair of DNA DSBs induced by VP-16 in AML cells and its possible mechanism. Methods The effects of BMS-345541 on the sensitivity of AML cells to VP-16 were determined by MTT. Flow cytome-try ( FCM) was applied to test the level of DNA dam-age, cell cycle progression and apoptosis in AML cells. High content analysis ( HCA) was used to verify the amount ofγ-H2AX,p-ATM,RAD51 in AML cells. Results BMS-345541 could significantly inhibit the proliferation of AML cells induced by VP-16 . BMS- <br> 345541 increased the amount of RAD51 foci and p-ATM foci in AML cells treated with VP-16 after 6 hours , which led to increased numbers of cells in the G2/M phases of the cell cycle,then induced apoptotic cell death. Conclusion BMS-345541 sensitizes AML cells to VP-16 via selective inhibition of homologous recombinational repair of DNA double-strand breaks.关键词
IKKβ/BMS-345541/DNA 损伤/γ-H2AX/p-ATM/RAD51Key words
IKKβ/BMS-345541/DNA damage/γ-H2 AX/p-ATM/RAD51分类
医药卫生引用本文复制引用
田崛,陈显凌,庄英婷,范莹娟,许建华,吴丽贤..BMS-345541对急性粒细胞白血病细胞DNA损伤修复的影响[J].中国药理学通报,2015,(6):763-768,769,7.基金项目
国家自然科学基金资助项目( No 30901824,81173096,81273541) ( No 30901824,81173096,81273541)
福建省自然科学基金杰出青年项目( No 2011J06013) ( No 2011J06013)
福建省高校跨世纪优秀人才项目( No JA11101) ( No JA11101)