Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone

In this study, we investigated the effects of luteinizing hormone- releasing hormone (LH-RH) agonist [D-Trp⁶]LH-RH, LH-RH antagonist [Ac-D- Na](2)¹, D-Phe(pCl)²,D-Pal(3)³,D-Cit⁶,D-Ala¹⁰]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 [³H]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-Trp⁶]LH-RH. In OV- 1063 cells, ¹²⁵I-labeled [D-Trp⁶]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). ¹²⁵I-labeled [D-Trp⁶]LH- RH could be displaced by unlabeled [D-Trp⁶]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°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.