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 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.
Damgé
C
C
Centre Européen d'Etude du Diabète, Hôpitaux Universitaires, Strasbourg, France.
Hajri
A
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001839:Bombesin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D019886:Gastrin-Releasing Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C091872:BIM 26226; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C060347:lanreotide; D014316:Tritium; D013004:Somatostatin; D019886:Gastrin-Releasing Peptide; D001839:Bombesin; D013936:Thymidine