Interferon gamma induces cell cycle arrest and apoptosis in a model of ovarian cancer: enhancement of effect by batimastat

Eur J Cancer. 1997 Jun;33(7):1114-21. doi: 10.1016/s0959-8049(97)88065-3.


Locoregional human IFN-gamma may have activity against refractory ovarian cancer. We investigated this further in an ovarian cancer xenograft model. Administered at clinically relevant doses, intraperitoneal IFN-gamma prolonged the survival of mice bearing multiple established peritoneal tumours, with optimal treatment giving a 3-6-fold increase in median survival time. Daily dosing, which was superior to intermittent treatment, decreased DNA synthesis and induced apoptosis in tumour cells with maximal effects after 7-21 days treatment. This was preceded by an increase in p53 protein at 48 h. The effect of IFN-gamma was not enhanced by sequential treatment with carboplatin. However, the matrix metalloprotease inhibitor, batimastat, further increased mouse survival when given after IFN-gamma. Thus IFN-gamma is cytotoxic to ovarian epithelial cells in vivo and intensive locoregional dosing over short periods is effective. Sequential administration of novel agents that perturb the host/tumour relationship may be of benefit.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects*
  • Carboplatin / administration & dosage
  • Cell Division / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / pathology
  • Cystadenocarcinoma, Serous / ultrastructure
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Humans
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / pharmacology
  • Metalloendopeptidases / antagonists & inhibitors
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / ultrastructure
  • Phenylalanine / administration & dosage
  • Phenylalanine / analogs & derivatives
  • Survival Rate
  • Thiophenes / administration & dosage
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / metabolism


  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Thiophenes
  • Tumor Suppressor Protein p53
  • Phenylalanine
  • Interferon-gamma
  • Carboplatin
  • batimastat
  • Metalloendopeptidases