GNRH AGONIST THERAPY IN HUMAN OVARIAN EPITHELIAL CARCINOMA (OVCAR-3) HETEROTRANSPLANTED IN THE NUDE-MOUSE IS CHARACTERIZED BY LATENCY AND TRANSIENCE

We have previously documented the responsiveness of a cell line of hum an ovarian epithelial carcinoma (Bowman Gray 1) heterotransplanted in nude mice to treatment with the GnRH agonist Lupron-SR. In this study we used another human ovarian epithelial carcinoma cell line, OVCAR-3, and the human endometrial carcinoma cell line HEC-1A. After a latent period, OVCAR-3 tumors showed significant inhibition of growth on Days 17, 21, and 24 (P < 0.03) compared to controls. The effect was transi ent and did not persist beyond Day 24. HEC-1A tumors showed no inhibit ion of growth. Radioreceptor assay studies utilizing native radiolabel ed GnRH and [D-Lys6]-GnRH revealed no specific GnRH receptors in any o f the tumor samples (BG-1, OVCAR-3, HEC-1A, University of Nebraska cel l line, and two fresh human ovarian epithelial tumor samples) compared to male rat anterior pituitary cells. Binding studies and the latency and transience of effect would suggest that the mechanism of action i n this animal model may be indirect. This activity may be via altered circulating steroids, gonadotropins, cell-cycle regulatory events, or some other as-yet-undefined action related to GnRH agonist administrat ion or indirectly via effects of the metabolic products of degraded Gn RH agonist such as D-amino acids, which are incorporated into the cell s by constitutive or adsorptive pinocytosis. This study confirms laten cy and transience of effect of GnRH agonist therapy on an in vivo mode l of ovarian cancer. (C) 1994 Academic Press, Inc.