title: ZM447439, the Aurora kinase B inhibitor, suppresses the growth of cervical cancer SiHa cells and enhances the chemosensitivity to cisplatin.
abstract: OBJECTIVE
  To investigate the effects of an Aurora kinase B inhibitor (ZM447439) on the cervical cancer cell line SiHa and chemotherapy of cisplatin (cDDP).
  
  
  METHODS
  Detected Aurora-B protein in different tissues of the cervix by immunohistochemistry and then analyzed the relationship between Aurora B protein and clinical parameters of cervical cancer. The effect and synergistic effect of ZM447439 and cDDP on proliferation of SiHa cells was tested by MTT. The changes of cell cycle and apoptosis were detected by flow cytometry. Aurora-B, histone H3 phosphorylation (H3-P) protein, human papillomavirus16 E6 (HPV16E6) and BCL-2, P53, VEGF protein were detected by Western blot.
  
  
  RESULTS
  The positive rate of Aurora-B expression was the highest in cervical cancer and had no significant correlation with clinical stage, lymph node metastasis and age. ZM447439 can reduce the number of SiHa cells, increase the volume of cells and lead to apoptosis. The growth of SiHa cells treated with ZM447439, cDDP and the combination of both was inhibited in dose- and time-dependent manners. The inhibition rate of the combined treatment is significantly higher than that of two other single drug groups (P < 0.05). The synergistic effect is observed in the combined therapy. S-phase arrest and early apoptosis has become more evident in the combined treatment. ZM447439 significantly inhibited the expression of Aurora-B and H3-P protein (P < 0.05). ZM447439, cDDP and the combination of both reduced the expression of HPV16E6 and BCL-2 protein, raised P53 protein expression (P < 0.05), whose effects were more obvious in the combined therapy. cDDP could also reduce VEGF protein expression, but ZM447439 could not.
  
  
  CONCLUSIONS
  Our results suggest that Aurora-B may represent a valid target in cervical squamous carcinoma and has a synergistic effect with cDDP.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China. zhangliya6912@163.com
authors.forename: Liya
authors.initials: L
authors.lastname: Zhang
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; D000970:Antineoplastic Agents; D001549:Benzamides; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin