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BMS-345541对急性粒细胞白血病细胞DNA损伤修复的影响

田崛 陈显凌 庄英婷 范莹娟 许建华 吴丽贤

中国药理学通报Issue(6):763-768,769,7.
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

田崛 1陈显凌 2庄英婷 3范莹娟 4许建华 5吴丽贤1

作者信息

  • 1. 福建医科大学药学院药理系,福建 福州 350004
  • 2. 福建省天然药物药理学重点实验室,福建 福州 350004
  • 3. 福建医科大学新药研究所,福建 福州 350004
  • 4. 福建医科大学附属协和医院血液科,福建 福州 350001
  • 5. 福建省血液病研究所,福建 福州 350001
  • 折叠

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/RAD51

Key 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)

中国药理学通报

OA北大核心CSCDCSTPCD

1001-1978

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