Biological and pharmacological characterisation of three models of human ovarian carcinoma established in nude mice: use of the CA125 tumour marker to predict antitumour activity.

ABSTRACT

In an attempt to improve the relevance of human tumour xenografts to the clinical situation, we have established 3 models of human ovarian carcinoma (IGROV1, A2780 and NIHOVCAR-3) in nude mice in which progressive peritoneal carcinomatosis resulted in the death of tumour-bearing animals (median survival times 32, 40 and 64 days, respectively). Histological analyses revealed both common and different characteristics in growth patterns and dissemination profiles. In each case, three stages of the disease were defined (early, intermediate and late). The antitumour activities of adriamycin, cisplatin, cyclophosphamide and paclitaxel were then compared when administered at the early stage where small multifocal tumour nodules were detectable in the peritoneal cavity of the animals. Significant antitumour activities of cisplatin and particularly paclitaxel were noted in terms of increase in survival time of the treated mice (T/C values for IGROV1, A2780 and NIHOVCAR-3 respectively 152%, 167%, and 187% for cisplatin and 211%, 179% and >283% for paclitaxel), paclitaxel being curative against the NIHOVCAR-3 xenograft. These results reflect the high efficacy of these two drugs in the clinic in the treatment of ovarian carcinoma. The clinically used CA125 tumour marker, not detectable in healthy mice, was measured in the serum of mice bearing IGROV1 and NIHOVCAR-3 tumours. CA125 serum levels increased as a function of time and were well correlated to disease progression. Moreover, treatment with cisplatin and paclitaxel led to significant decreases in these levels of between 58% and 100%. This human serum marker could be used to predict early on the efficacy of chemotherapy in these two models. In conclusion, the three experimental ovarian carcinomas possess several important characteristics of the human disease and may thus be used as a screen to select new antitumour drugs potentially active in this pathology.