INHIBITION OF HUMAN EPITHELIAL OVARIAN-CANCER CELL-GROWTH IN-VITRO BY AGONISTIC AND ANTAGONISTIC ANALOGS OF LUTEINIZING-HORMONE-RELEASING HORMONE

In this study, we investigated the effects of luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp(6)]LH-RH, LH-RH antagonist [Ac-D-Nal(2)(1),D-Phe(pCl)(2),D-Pal(3)(3),D-Cit(6),D-Ala(10)]LH-RH (SB-75), and estradiol on the growth of human epithelial ovarian cancer cell line OV-1063. Cells were cultured under estrogen-deprived conditions. Estradiol inhibited cell proliferation, as measured by cell number at 10(-9)-10(-7) M and [H-3]thymidine incorporation into DNA at 10(-13)-10(-8) M. Both LH-RH analogs inhibited cell growth dose dependently in the range 10(-8)-10(-5) M, but SB-75 induced a greater growth inhibition than [D-Trp(6)]LH-RH. In OV-1063 cells, I-125-labeled [D-Trp(6)]LH-RH was bound to one class of specific, saturable binding sites with high affinity (K-d = 1.4 +/- 0.3 nM) and low capacity (4000 binding sites per cell). I-125-labeled [D-Trp(6)]LH-RH could be displaced by unlabeled [D-Trp(6)]LH-RH and SB-75, suggesting that both analogs are bound to the same receptor on OV-1063 cells. Ligand binding was dependent on time and temperature. Receptor internalization assay showed that the ligand-receptor complex was internalized at 37 degrees C, which indicates the presence of biologically active LH-RH receptors on OV-1063 cells. These results suggest that estradiol and LH-RH analogs can suppress the growth of OV-1063 human epithelial ovarian cancer cells by a direct action and that the inhibitory effect of LH-RH analogs is mediated through the high-affinity LH-RH receptors.