title: Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells.
abstract: OBJECTIVE
  To evaluate the efficacy of combination of navitoclax, carboplatin and paclitaxel in ovarian cancer.
  
  
  METHODS
  8 ovarian cancer cell lines were treated with either doublet or triplet combinations of navitoclax, carboplatin and paclitaxel. Interactions were assessed by determining a combination index or measuring caspase activity. The effect of the combinations was also evaluated by measuring the inhibition of cells grown as spheroids.
  
  
  RESULTS
  Navitoclax exhibited modest (IC(50)=3-8 μM) single agent potency. Antagonism between carboplatin and paclitaxel was evident in Ovcar-4, Ovcar-8 and Skov-3 cells. Drug combinations including navitoclax with carboplatin and/or paclitaxel showed significantly less antagonism, or even synergy, in several cell lines than carboplatin/paclitaxel alone. Navitoclax enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells. Combinations of navitoclax, carboplatin and paclitaxel showed more than additive activity against Igrov-1 spheroids.
  
  
  CONCLUSIONS
  Navitoclax improves the activity of combinations of carboplatin and paclitaxel in vitro. Our observations, taken with other published data, provide a rationale for clinical trials of navitoclax in ovarian cancer in combination with chemotherapy.
authors.affiliation: Institute for Science and Technology in Medicine, Guy Hilton Research Centre, Keele University, Thornburrow Drive, Stoke-on-Trent, ST4 7QB, UK.
authors.forename: Vasileios A
authors.initials: VA
authors.lastname: Stamelos
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Robinson
authors.forename: Charles W
authors.initials: CW
authors.lastname: Redman
authors.forename: Alan
authors.initials: A
authors.lastname: Richardson
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000814:Aniline Compounds; D013449:Sulfonamides; D016190:Carboplatin; D017239:Paclitaxel; C528561:navitoclax