Inhibition of growth of a transplanted rat pancreatic acinar carcinoma with CCK-8.
Gastrointestinal hormones and neuropeptides are known to regulate growth of various normal gastrointestinal tissues and many cancers. Since cholecystokinin (CCK) is considered the most potent trophic factor for the exocrine pancreas, we studied its effect on growth of an acinar cell tumor, initially induced by azaserine and transplanted to the rat, in comparison with the normal pancreas. When tumors became palpable, rats were treated three times daily for 12 or 14 days with CCK-8 or NaCl 0.9% (controls) alone or in combination with the CCK receptor antagonist CR1409 (10 mg/kg) administered subcutaneously twice daily. Then tumors and pancreata were analyzed for their size, composition, and CCK receptors. Tumor volume, weight, and protein content, RNA, DNA, and enzymes decreased after CCK-8 treatment in a dose-dependent manner, the maximal effect being observed with 4-micrograms/kg treatment. This inhibitory effect was partially suppressed by CR1409, which by itself also reduced tumor growth, but to a lesser degree. CCK-8 exerted a stimulating effect on growth of the normal pancreas with low doses (1 and 2 micrograms/kg) and an inhibitory effect or no effect with a higher dose (4 micrograms/kg). CR1409 prevented this latter effect, but did not affect by itself the normal pancreas. These findings suggest that CCK-8 inhibits growth of an acinar cell tumor grafted to the rat; this effect is mediated by the occupation of specific CCK receptors present in high density on these cells. In contrast, CCK-8 exerts a biphasic effect on the normal pancreas as a function of its dose.
Karsenty
L
L
INSERM U61, Biologie Cellulaire et Physiopathologie Digestives, Strasbourg, France.
Hajri
A
A
Aprahamian
M
M
Garaud
J C
JC
Doffoël
M
M
Damgé
C
C
D000818:Animals; D002277:Carcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000627:therapeutic use*
D011949:Receptors, Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide