Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells

Gynecol Oncol. 2013 Feb;128(2):377-82. doi: 10.1016/j.ygyno.2012.11.019. Epub 2012 Nov 17.


Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / administration & dosage
  • Aniline Compounds / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacology*
  • Cell Line, Tumor
  • Drug Interactions
  • Drug Synergism
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*


  • Aniline Compounds
  • Sulfonamides
  • Carboplatin
  • Paclitaxel
  • navitoclax