INTERFERON-GAMMA INDUCES CELL-CYCLE ARREST AND APOPTOSIS IN A MODEL OF OVARIAN-CANCER - ENHANCEMENT OF EFFECT BY BATIMASTAT

Locoregional human IFN-gamma may have activity against refractory ovar ian cancer. We investigated this further in an ovarian cancer xenograf t model. Administered at clinically relevant doses, intraperitoneal IF N-gamma prolonged the survival of mice bearing multiple established pe ritoneal tumours, with optimal treatment giving a 3-6-fold increase in median survival time. Daily dosing, which was superior to intermitten t treatment, decreased DNA synthesis and induced apoptosis in tumour c ells 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 no t enhanced by sequential treatment with carboplatin. However, the matr ix metalloprotease inhibitor, batimastat, further incrased mouse survi val 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. (C) 1997 Elsev ier Science Ltd.