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

摘要

In this study, we investigated the effects ofluteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, LH-RHantagonist [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), andestradiol on the growth of human epithelial ovarian cancer cell line OV-1063.Cells were cultured under estrogen-deprived conditions. Estradiol inhibited cellproliferation, as measured by cell number at 10(-9)-10(-7) M and [3H]thymidineincorporation into DNA at 10(-13)-10(-8) M. Both LH-RH analogs inhibited cellgrowth dose dependently in the range 10(-8)-10(-5) M, but SB-75 induced agreater 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 withhigh affinity (Kd = 1.4 +/- 0.3 nM) and low capacity (4000 binding sites percell). 125I-labeled [D-Trp6]LH-RH could be displaced by unlabeled [D-Trp6]LH-RHand SB-75, suggesting that both analogs are bound to the same receptor onOV-1063 cells. Ligand binding was dependent on time and temperature. Receptorinternalization assay showed that the ligand-receptor complex was internalizedat 37 degrees C, which indicates the presence of biologically active LH-RHreceptors on OV-1063 cells. These results suggest that estradiol and LH-RHanalogs can suppress the growth of OV-1063 human epithelial ovarian cancer cellsby a direct action and that the inhibitory effect of LH-RH analogs is mediatedthrough the high-affinity LH-RH receptors.