Abstract
We investigated the effects of bombesin/GRP antagonists RC‐3095 and RC‐3940‐II on the growth of SW‐1990 human pancreatic adenocarcinoma cells xenografted into nude mice or cultured in vitro. Nude mice implanted with SW‐1990 tumors received s.c. injections of RC‐3095 and RC‐3940‐II or the vehicle (control) for 28 days. Chronic administration of RC‐3940‐II inhibited the growth of SW‐1990 tumors, as shown by a reduction in tumor volume during the treatment and a significant increase in tumor doubling time. RC‐3940‐II decreased final tumor volume by 57.7% and tumor growth rate by 65%. Final tumor weights in mice treated with RC‐3940‐II were 75% lower than in controls. Treatment with RC‐3095 induced smaller, and not significant, decreases in tumor volume and weight. In cell cultures, both RC‐3095 and RC‐3940‐II effectively inhibited the proliferation of SW‐1990 cells, inducing a dose‐ and time‐dependent decrease in the number of cells. RC‐3940‐II again suppressed in vitro growth of SW‐1990 cells more effectively than RC‐3095. After 72 hr of culture, RC‐3940‐II and RC‐3095 at I μM concentrations decreased cell numbers by 45.7% and 27.7%, respectively. The estimated EC~50~ value for RC‐3940‐II was I nM. When SW‐1990 cells were cultured in the presence of I nM and 10 nM RC‐3095 for 72 hr, cAMP levels in the incubation medium were decreased to 77.3% and 26.9% of the control value. Our results indicate that bombesin/GRP antagonist RC‐3940‐II can inhibit the proliferation of SW‐1990 human pancreatic adenocarcinoma cells in vivo and in vitro. Our findings also suggest that this effect may involve the intracellular cAMP pathway.