Female Syrian golden hamsters with N-nitrosobis(2-oxopropyl)amine-induced
pancreatic cancers were treated for 2 months with new pseudononapeptide
bombesin receptor antagonist [D-Tpi6,Leu13 psi (CH2NH)-Leu14]
bombesin(6-14)(
RC-3095), administered s.c. with implanted osmotic minipumps releasing 20 micrograms/day of the analogue. The results were compared to those obtained by treatment with
somatostatin analogue
RC-160 (35 micrograms/day and 150 micrograms/day) or [D-Trp6]
luteinizing hormone-releasing hormone (25 micrograms/day), which inhibited the growth of
pancreatic cancers in our previous studies. A new acetylated
somatostatin analogue [formula: see text] (30 micrograms/day) also was used for comparison of therapeutic response. All
peptide analogues induced
tumor inhibition by at least one of the measured parameters.
Bombesin antagonist
RC-3095 and high dose of
RC-160 (150 micrograms/day) had the greatest inhibitory effect on
pancreatic cancers: A significant decrease in the number of animals with
tumors, reduced pancreatic weight, 87-89% inhibition of tumorous pancreas weight, and a significant diminution in the number of
tumor nodules and argyrophilic nucleolar organizer region count in
tumor cell nuclei were observed in the groups treated with these regimens. We were able to detect receptors for
bombesin in membranes of N-nitrosobis(2-oxopropyl)amine-induced pancreatic
tumors and these receptors were not down-regulated
after treatment with the
bombesin antagonist. In hamsters treated with
bombesin antagonists,
tumor inhibition might be explained by a significant decrease in the binding capacity of
epidermal growth factor receptors in
pancreatic cancers. The acetylated
somatostatin analogue RC-160-II had a similar inhibitory effect on the
tumors as the original analogue
RC-160. Our results suggest that the increase in the dose of
RC-160 improves the therapeutic response, and this finding should be taken into account in clinical use of this
somatostatin analogue. In view of its strong inhibitory effect on experimental pancreatic
tumors, the
bombesin antagonist
RC-3095 might be considered as a possible new agent for the
therapy of human exocrine
pancreatic cancer.