Bombesin inhibits growth of human pancreatic adenocarcinoma in nude mice.
Bombesin, a 14-amino acid peptide, exhibits direct and indirect effects on the gastrointestinal tract, including release of hormones, stimulation of pancreatic, gastric, and intestinal secretion and intestinal motility. Cholecystokinin (CCK) and gastrin, two of the hormones released by bombesin, have been shown to play a role in maintaining the growth of normal gastrointestinal mucosa as well as in eliciting trophic responses in normal and neoplastic tissue. We studied the effects of chronic bombesin treatment on the growth of a human ductal pancreatic adenocarcinoma (SKI) xenografted into nude mice, and on the growth of the normal nude mouse pancreas. Thirteen nude mice were implanted with SKI tumor and divided into two groups. Mice received 0.1 ml intraperitoneal injections of either bombesin (20 micrograms/kg) or the vehicle alone three times per day. Tumor areas were measured twice weekly until death (week 8), at which time the tumors and the host pancreas were excised, weighed, and assayed for protein, RNA, and DNA content. Significant inhibition of tumor growth was found in the bombesin-treated group at weeks 4, 5, 6, 7, and 8. Tumor area and weight at death (day 57) were significantly less in the bombesin-treated group (48 and 46%) as compared with control. We observed similar inhibition of tumor DNA (39%), RNA (38%), and protein (43%) content compared with controls. In contrast, bombesin significantly increased the weight (64%), protein (81%), and DNA (73%) content of the mouse pancreas compared with controls. We conclude that bombesin acts concurrently as both a trophic agent for normal host pancreas and a growth inhibitory agent in xenografted pancreatic cancer tissue.
Alexander
R W
RW
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Upp
J R
JR
Poston
G J
GJ
Townsend
C M
CM
Singh
P
P
Thompson
J C
JC
D000818:Animals; D001839:Bombesin / Q000627:therapeutic use*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000378:metabolism; D014183:Transplantation, Heterologous
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D001839:Bombesin