title: [Effect of aurora kinase B inhibitor AZD1152 in the treatment of cisplatin-resistant ovarian carcinoma].
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 in-situ 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 inhibit ovarian cancer cells proliferation and induce cells apoptosis significantly. AZD alone or in combination with cisplatin may result in the increased cells polyploidy.
authors.affiliation: Department of Gynecology, Zhejiang University, Hangzhou, China. ma_zeyy@sohu.com
authors.forename: Ya-xi
authors.initials: YX
authors.lastname: Ma
authors.forename: Xiu-zhen
authors.initials: XZ
authors.lastname: Li
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D010755:Organophosphates / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D010755:Organophosphates; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D019098:Telomerase; D002945:Cisplatin