Lh-rh and its antagonist cetrorelix inhibit growth of jar human choriocarcinoma cells in-vitro.

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-Cit(6),D-Ala(10)]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 SE-75, at 1 mu g concentration, inhibited the growth of JAR cells in cultures. When SE-75 (1 mu M) was given in combination with different doses (0.1 nM to 1 mu M) of LH-RH, it was found that 0.1 nM LH-RH nullified the inhibitory effect of SE-75 on cell growth, however, the 100 nM and 1 mu M doses of LH-RH caused a greater inhibition of cell proliferation than SE-75 alone. Incubation with LH-RH slightly increased the hCG production and the cAMP release in the cultured tumor cells. SE-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 mu M SE-75, on the cAMP production, was similar to that on cell growth: 0.1 nM LH-RH in combination with 1 mu M SE-75 caused a smaller inhibition of cAMP than SE-75 alone. However, when LH-RH was given at concentrations from 1 nM to 1 mu M together with 1 mu M SE-75, we observed a greater inhibition of cAMP than after SE-75 alone. The presence of low affinity LH-RH receptors on JAR cells was also demonstrated and competitive binding studies showed that agonist D-Trp(6)-LH-RH and antagonist SE-75 could bind to these receptors. Our findings provide new information on the effect of LH-RH and antagonist SE-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.