Effect Of BMS-345541 On The Repair Of DNA Double-strand Breaks In Acute Myeloid Leukemia Cells

Purpose To investigate the effect and its possible mechanism of BMS-345541 on the repair of DNA DSBs induced by VP-16 in AML cells.Methods The effects of BMS-345541 on the sensitivity of AML cells to VP-16 were determined by MTT; the level of DNA damage, cell cycle progression and apoptosis in AML cells were tested by Flow Cytometry(FCM); High Content Analysis(HCA) was used to verified the amount of γ-H2AX、p-ATM、RAD51 in AML cells. The m RNA level of ATM was examined by Real-time PCR. Western blot was used to detect DNA damage related protein level.Result(1)BMS-345541 can significantly inhibit the proliferation of AML cells treated with VP-16.(2)BMS-345541 increased the amount of γ-H2 AX foci in AML cells and LSC treated with VP-16.(3)VP-16 can significantly blocked AML cells in the G2/M phase of the cell cycle.This phenomenon will be inhibited while add BMS-345541.(4)The group which combined VP-16 and BMS-345541 increased the apoptosis rate more than VP-16 treated only.(5)BMS-345541 increased the amount of RAD51 foci and p-ATM foci in AML cells treated with VP-16 after 6 hours.(6)The expression of ATM in combination group was raised more than repair group tested by Real-Time PCR.(7)DNA damage related protein level raised in combination group.Conclusion BMS-345541 can inhibit the repair of DNA Double-Strand Breaks include by VP-16 in AML cells by selective inhibition of homologous recombinational Repair.