EFFECTS OF GNRH ANALOGS ON 6 OVARIAN-CANCER CELL-LINES IN CULTURE

The objective was to evaluate the possible direct anti-tumor effects o f the GnRH agonists buserelin and leuprolide acetate and the GnRH anta gonist antide on ovarian cancer cell lines in culture. Evidence from s everal hormone-responsive tumor systems suggests that GnRH analogs may have direct anti-tumor effects at the cellular level. In small clinic al trials, the use of GnRH analogs in advanced refractory ovarian canc er has produced some dramatic responses. With this in mind, we evaluat ed the growth effects of the GnRH agonists buserelin and leuprolide an d the GnRH antagonist antide over a range of concentrations on six est ablished ovarian cancer cell lines over a period of 7 days. Cell viabi lity was measured by an ATP-bioluminescence assay and expressed as a p ercentage of untreated control cultures. Analysis of variance was used to evaluate significant growth differences from control cultures. Alt hough we were able to demonstrate statistically significant reduction in cell growth in two of six cell lines with buserelin, no dose-relate d response patterns were seen. While buserelin caused a maximum 16% in hibition of growth, antide had no effect on tumor growth at the same d oses. Leuprolide acetate produced significant dose-dependent inhibitio n of growth in all six cell lines when doses were increased to supraph ysiologic levels, but demonstrated no significant inhibition at doses that are clinically attainable. Furthermore, competitive binding assay s showed no specific GnRH binding in any of the six ovarian cell lines tested. Although GnRH analogs have growth inhibitory effects on ovari an cancer cells in vitro, the magnitude of this effect at doses that a re clinically achievable is insufficient to support direct tumor effec ts as the mechanism behind the clinical responses reported. (C) 1994 A cademic Press, Inc.