Antagonists of bombesin/gastrin-releasing Peptide inhibit growth of jar human choriocarcinoma cells and production of cyclic-amp in-vitro

The effects of bombesin/GRP antagonists RC-3095 and RC-3940-II on the in vitro proliferation of JAR human choriocarcinoma cells were evaluated. Antagonists RC-3095 and RC-3940-II effectively inhibited growth of cultured JAR cells, inducing a dose- and time-dependent decrease in the number of treated cells. RC-3940-II was more potent than RC-3095 in inhibiting the growth of JAR cells. Addition of RC-3940-II to JAR cell cultures significantly inhibited the cell proliferation at concentrations as low as 1 nM, while 10 nM RC-3095 was required for a similar effect. Receptor binding studies demonstrated the presence of a single class of binding sites for bombesin on JAR cells. RC-3940-II displaced [I-125]Tyr(4)-bombesin bound to the receptors. When JAR cells were cultured in the presence of 10 nM RC-3095 or RC-3940-II for 72 h, cAMP levels in the incubation medium were decreased by 70-80%, compared to the controls. These results suggest that bombesin/GRP antagonists RC-3095 and RC-3940-II inhibit the proliferation of JAR human chorionic adenocarcinoma cells in vitro and that these effects may involve intracellular cAMP pathway.