BMS-345541 regulates repair of DNA double-strand breaks induced by VP-16 in acute myeloid leukemia cells

VernacularTitle:BMS-345541对急性粒细胞白血病细胞DNA损伤修复的影响
Author: Jue TIAN ; Xianling CHEN ; Yingting ZHUANG ; Yingjuan FAN ; Jianhua XU ; Lixian WU
Publication Type:Journal Article
Keywords: IKKβ; BMS-345541; DNA damage; γ-H2 AX; p-ATM; RAD51
From: Chinese Pharmacological Bulletin 2015;(6):763-768,769
CountryChina
Language:Chinese
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.