EFFECT OF THE GASTRIN-RELEASING PEPTIDE ANTAGONIST BIM-26226 AND LANREOTIDE ON AN ACINAR PANCREATIC-CARCINOMA

The effects of a potent specific gastrin-releasing peptide receptor an tagonist, BIM 26226 ([D-F-5 Phe(6), D-Ala(11)] bombesin (6-13) OMe), a nd the long-acting somatostatin analogue, lanreotide (BIM 23014), on t he 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 mu g/kg per day), BIM 26226 (30 and 100 mu g/kg per day) and lanreotide (100 mu g/kg per day) alone or in comb ination for 14 successive days. Chronic administration of BIM 26226 an d lanreotide significantly inhibited the growth of pancreatic tumours stimulated or not by gastrin releasing peptide (GRP), as shown by a re duction in tumour volume, protein, ribonucleic acid, amylase and chymo trypsin contents. This effect was more pronounced with 100 mu g/kg per day BIM 26226 than with 30 mu g/kg per day. However, BIM 26226 and la nreotide, given together, did not exert any additive effect on GRP-tre ated and -untreated tumours. In cell cultures, both BIM 26226 and lanr eotide (10(-6) M) inhibited [H-3]thymidine incorporation in tumour cel ls induced or not by GRP, but no increased effect was observed after c ombined treatment with both agents. Binding studies showed that BIM 26 226 had a high affinity for GRP receptors in tumour cell membranes (IC 50 = 6 nM). These results from in vivo and in vitro experiments sugges t that BIM 26226 and lanreotide are able to reduce the growth of an ex perimental acinar pancreatic tumour. Thus, these agents represent inte resting steps toward the development of new approaches for treatment o f pancreatic carcinomas. (C) 1998 Elsevier Science B.V.