Effect of aurora kinase B inhibitor AZD1152 in the treatment of cisplatin-resistant ovarian carcinoma / 中华妇产科杂志

ABSTRACT

Objective To investigate whether AZD1152 (AZD),the selective inhibitor of aurora kinase B,may play a role in the treatment of cisplatin-resistant ovarian carcinoma when administrated alone or in combination with cisplatin.Methods Hey (cisplatin-resistant ovarian cancer cell line) cells were analyzed.According to the treatment plan,Hey cells were divided into four groups (AZD group,cisplatin group,AZD + cisplatin group and control group).Methyl thiazolyl tetrazolium (MTT) assay was used to test the cells proliferation,caspase-3/7 activity analysis was used to analyze cells apoptosis,and fluorescence insitu hybridization (FISH) assay was used to determine the copy the number of chromosome 7 and checked the copy numbers of hTERC gene and C-myc gene.Results MTT test showed that proliferation of AZD group was lower than that in control group(P ＜ 0.01).The cells proliferation with the treatment with 10 and 20 nmol/L AZD for 24 hours was (81.4 ± 3.6)％ and (81.4 ± 3.6)％ respectively,and the cells proliferation for 48 hours was (43.1 ± 2.0) ％ and (38.5 ± 1.6) ％ respectively,which was significantly lower than control group (100％,P ＜ 0.01) ; Treated with the same concentration of AZD,inhibition of proliferation was significantly enhanced as the time extended (P ＜ 0.01).Proliferation in group AZD+cisplatin was lower than that in cisplatin group (P ＜ 0.01) which suggest that there were additive effects after combined AZD with cisplatin.Compared with control group,caspase-3/7 activity in AZD group increased significantly (P =0.000),and the same results was seen between AZD ± cisplatin group and cisplatin group or AZD group (all P ＜ 0.01).Compared with cisplatin group or control group,the copy numbers of hTERC,C-myc and the number of chromosome were significantly increased in AZD group and AZD + cisplat group (all P ＜ 0.05).Conclusions AZD could inhibite ovarian cancer cells proliferation and induce cells apoptosis significantly.AZD alone or in combination with cisplatin may result in the increased cells polyploidy.