Effect of cholecystokinin analogue caerulein and cholecystokinin antagonist lorglumide on pancreatic carcinogenesis in the rat.
The effects of the cholecystokinin (CCK)-analogue, caerulein, and CCK-receptor antagonist lorglumide (CR-1409) on pancreatic carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) were studied. One hundred thirty rats were divided into the following 10 treatment groups: group 1, DMBA (2-3 mg); group 2, DMBA + caerulein (5 micrograms/kg); group 3, DMBA + caerulein + CR-1409 (12 mg/kg); group 4, caerulein + DMBA; group 5, caerulein + CR-1409 + DMBA; group 6, DMBA + CR-1409; group 7, CR-1409 + DMBA; group 8, caerulein; group 9, CR-1409; and group 10, sham operation + saline. DMBA was surgically implanted into the pancreas. Caerulein and/or CR-1409 was administered twice daily for 15 days after (in groups 2, 3, and 6) or before (in groups 4, 5, and 7) DMBA implantation. Six months after carcinogen administration, all rats were sacrificed and autopsied. The incidence of pancreatic cancer appeared significantly (P < 0.001) increased when caerulein was administered following DMBA implantation. CR-1409 significantly inhibited (P < 0.02) caerulein effects and reduced tumor growth when injected after carcinogen exposure.
Sperti
C
C
Department of Surgery, University of Padua, Italy.
Militello
C
C
Rovati
L
L
Behboo
R
R
Khajeturian
E
E
Perasole
A
A
Alaggio
R
R
Pedrazzoli
S
S
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002108:Ceruletide / Q000494:pharmacology*; D016009:Chi-Square Distribution; D004273:DNA, Neoplasm / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D004273:DNA, Neoplasm; D011949:Receptors, Cholecystokinin; D015127:9,10-Dimethyl-1,2-benzanthracene; D002108:Ceruletide; D011377:Proglumide; C048181:lorglumide