Effects of GnRH analogs on six ovarian cancer cell lines in culture.
The objective was to evaluate the possible direct anti-tumor effects of the GnRH agonists buserelin and leuprolide acetate and the GnRH antagonist antide on ovarian cancer cell lines in culture. Evidence from several hormone-responsive tumor systems suggests that GnRH analogs may have direct anti-tumor effects at the cellular level. In small clinical trials, the use of GnRH analogs in advanced refractory ovarian cancer has produced some dramatic responses. With this in mind, we evaluated the growth effects of the GnRH agonists buserelin and leuprolide and the GnRH antagonist antide over a range of concentrations on six established ovarian cancer cell lines over a period of 7 days. Cell viability was measured by an ATP-bioluminescence assay and expressed as a percentage of untreated control cultures. Analysis of variance was used to evaluate significant growth differences from control cultures. Although we were able to demonstrate statistically significant reduction in cell growth in two of six cell lines with buserelin, no dose-related response patterns were seen. While buserelin caused a maximum 16% inhibition of growth, antide had no effect on tumor growth at the same doses. Leuprolide acetate produced significant dose-dependent inhibition of growth in all six cell lines when doses were increased to supraphysiologic levels, but demonstrated no significant inhibition at doses that are clinically attainable. Furthermore, competitive binding assays showed no specific GnRH binding in any of the six ovarian cell lines tested. Although GnRH analogs have growth inhibitory effects on ovarian cancer cells in vitro, the magnitude of this effect at doses that are clinically achievable is insufficient to support direct tumor effects as the mechanism behind the clinical responses reported.
Department of Obstetrics and Gynecology, University of Iowa, College of Medicine, Iowa City 52242.
J P
JP
Connor
R E
RE
Buller
P M
PM
Conn
D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002064:Buserelin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016729:Leuprolide / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007986:Luteinizing Hormone / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured
D007986:Luteinizing Hormone; D016729:Leuprolide; D002064:Buserelin