Abstract. The effects of luteinizing hormone-releasing hormone (LH-RH), and LH-RH antagonist Cetrorelix, (SB-75, [Ac-D-Nal(2)1,D-Phe(4-Cl)2,D-Pal(3)3,D-Cit6, D- Ala10]LH-RH) on cell growth and the production of hCG and cAMP in JAR human choriocarcinoma cells were examined in vitro. Both LH-RH and its antagonist SB-75, at 1 μg concentration, inhibited the growth of JAR cells in cultures. When SB-75 (1 μM) was given in combination with different doses (0.1 nM to 1 μM) of LH-RH, it was found that 0.1 nM LH-RH nullified the inhibitory effect of SB-75 on cell growth, however, the 100 nM and 1 FtM doses of LH-RH caused a greater inhibition of cell proliferation than SB-75 alone. Incubation with LH-RH slightly increased the hCG production and the cAMP release in the cultured tumor cells. SB-75 alone or in combination with LH-RH reduced the hCG as well as the cAMP release from JAR human choriocarcinoma cells; however, the magnitude of the decrease was smaller for hCG than for cAMP. The effect of different doses of LH-RH, administered simultaneously with 1 μM SB-75, on the cAMP production, was similar to that on cell growth: 0.1 nM LH-RH in combination with 1 μM SB-75 caused a smaller inhibition of cAMP than SB-75 alone. However, when LH-RH was given at concentrations from 1 nM to 1 μM together with 1 μM SB-75, we observed a greater inhibition of cAMP than after SB-75 alone. The presence of low affinity LH-RH receptors on JAR cells was also demonstrated and competitive binding studies showed that agonist D-Trp6-LH-RH and antagonist SB-75 could bind to these receptors. Our findings provide new information on the effect of LH-RH and antagonist SB-75 on the proliferation of JAR human choriocarcinoma cells and may offer a new insight on their mechanisms of action in the suppression of tumor cell growth and their influence on intracellular signal transduction pathways. Hormonal therapy based on Cetrorelix could be considered for the development of new approaches to treatment of patients with choriocarcinomas.
|Number of pages||7|
|Journal||International Journal of Oncology|
|State||Published - Jan 1 1995|