Aurora Kinase B Selective Inhibitor Azd1152 Treatment Of Acute Leukemia In Experimental Research

Objective: To study AZD1152,a selective Aurora B kinase inhibitor, induces growth arrest, apoptosis in acute human leukemia cells,such as, (acute lymphyblastic leukemia,ALL)PALL-2 and (acute monocytic leukemia,AMoL)MOLM13.Methods:1 The effect of AZD1152 on cologenic growth of MOLM13 as well as normal bone marrow mononuclear cells were assessed by colony-forming assay.2 Cell cycle analysis was performed on PALL-2 and MOLM13 with various concentrations of AZD1152 or various cultured time with the drug by flow cytometry.3 The ability of AZD1152 to induce apoptosis of MOLM13 was mearsured with various concentrations of AZD1152 or various cultured time with the drug by flow cytometry.4 The ability of AZD1152 to induce the level of cleaved PARP was preformed on PALL-2 and MOLM13 by immunoblotting.Results:1 AZD1152 inhibited the clonogenic growth of MOLM13 and bone marrow mononuclear cells from healthy volunteers were less than 3nM and more than 10nM,respectively.AZD1152 effective inhibited the ability of colony forming of MOLM13 compared with normal bone marrow mononuclear cells(P<0.01).2 With the same time,the percent of the polyploid of MOLM13 and PALL-2 cells exposed to AZD1152 was increased with the increasement of the dose, compared with AZD1152 0nM group(P<0.01); the percent of the polyploid of MOLM13 and PALL-2 cells exposed to AZD1152 was increased with time progongation at the same dose. In one word,exposure of MOLM13 and PALL-2 cells to AZD1152 prominently increased cell DNA content in a time- and dose-dependent manner(P<0.01).3 A ZD1152 induced apoptosis in MOLM13 and PALL-2 in a dose-dependent manner, compared with untreated controls(P<0.05). 4 Exposure of MOLM13 and PALL-2 cells to AZD1152 for 12h induced cleavage of PARP,besides,the level of the cleavage of PARP was enchanced by the increasement of the dose of AZD1152.Conclusions:1 AZD1152 effective inhibited the ability of colony forming of MOLM13 compared with normal bone marrow mononuclear cells.2 AZD1152,a selective Aurora B kinase inhibitor, induces growth arrest, increases DNA content and induces apoptosis in MOLM13 and PA LL-2 cells.