The effects of a potent specific
gastrin-releasing peptide receptor antagonist,
BIM 26226 ([D-F5 Phe6, D-Ala11]
bombesin (6-13) OMe), and the long-acting
somatostatin analogue,
lanreotide (
BIM 23014), on the growth of an acinar pancreatic
adenocarcinoma growing in the rat or cultured in vitro were investigated. Lewis rats bearing a
pancreatic carcinoma transplanted s.c. in the scapular region, were treated with
gastrin-releasing peptide (30 microg/kg per day),
BIM 26226 (30 and 100 microg/kg per day) and
lanreotide (100 microg/kg per day) alone or in combination for 14 successive days. Chronic administration of
BIM 26226 and
lanreotide significantly inhibited the growth of pancreatic tumours stimulated or not by
gastrin-releasing peptide (GRP), as shown by a reduction in tumour volume,
protein,
ribonucleic acid,
amylase and
chymotrypsin contents. This effect was more pronounced with 100 microg/kg per day
BIM 26226 than with 30 microg/kg per day. However,
BIM 26226 and
lanreotide, given together, did not exert any additive effect on GRP-treated and -untreated tumours. In cell cultures, both
BIM 26226 and
lanreotide (10(-6) M) inhibited [3H]
thymidine incorporation in tumour cells induced or not by GRP, but no increased effect was observed after combined treatment with both agents. Binding studies showed that
BIM 26226 had a high affinity for GRP receptors in tumour cell membranes (IC50 = 6 nM). These results from in vivo and in vitro experiments suggest that
BIM 26226 and
lanreotide are able to reduce the growth of an experimental acinar pancreatic tumour. Thus, these agents represent interesting steps toward the development of new approaches for treatment of
pancreatic carcinomas.