CAJ | 학술논문

目的：体外研究 BMS-345541对急性粒细胞白血病( AML)细胞DNA损伤修复的影响及其可能的作用机制。方法 MTT 法检测 VP-16作用于 AML 细胞,加入或不加入BMS-345541对该细胞增殖抑制的影响；流式细胞术检测BMS-345541对AML细胞DNA损伤修复、细胞周期阻滞和细胞凋亡的影响；高内涵观察不同处理组γ-H2AX、p-ATM、RAD51募集在断裂位点的焦点情况。结果联合用药组比单用VP-16组对细胞的增殖抑制作用强；流式检测加入BMS-345541组比不加入组的γ-H2AX比例高,且加入BMS-345541组能够抑制VP-16导致的AML细胞G2/M期阻滞,增加细胞的凋亡率；高内涵检测断裂位点的 p-ATM 及RAD51的荧光焦点,6 h后,加入BMS-345541组比修复组的焦点的平均荧光强度和平均荧光面积高。结论 VP-16导致AML细胞产生DNA损伤,加入BMS-345541,能通过抑制HR通路来抑制细胞DNA损伤修复。
목적：체외연구 BMS-345541대급성립세포백혈병( AML)세포DNA손상수복적영향급기가능적작용궤제。방법 MTT 법검측 VP-16작용우 AML 세포,가입혹불가입BMS-345541대해세포증식억제적영향；류식세포술검측BMS-345541대AML세포DNA손상수복、세포주기조체화세포조망적영향；고내함관찰불동처리조γ-H2AX、p-ATM、RAD51모집재단렬위점적초점정황。결과연합용약조비단용VP-16조대세포적증식억제작용강；류식검측가입BMS-345541조비불가입조적γ-H2AX비례고,차가입BMS-345541조능구억제VP-16도치적AML세포G2/M기조체,증가세포적조망솔；고내함검측단렬위점적 p-ATM 급RAD51적형광초점,6 h후,가입BMS-345541조비수복조적초점적평균형광강도화평균형광면적고。결론 VP-16도치AML세포산생DNA손상,가입BMS-345541,능통과억제HR통로래억제세포DNA손상수복。
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.