Effects of cholecystokinin octapeptide on a pancreatic acinar carcinoma in the rat.
OBJECTIVE
To investigate the effects of increasing concentrations of cholecystokinin octapeptide (CCK-8) on a pancreatic acinar adenocarcinoma.


METHODS
Growth of the tumour was estimated in vivo on rats bearing a subcutaneous pancreatic carcinoma, and in vitro on primary cultured tumour cells. CCK receptors were characterized by binding assays.


RESULTS
CCK-8, administered for 12 successive days, exerted a biphasic action on tumour growth: a dose-dependent stimulation with low doses (0.1 and 0.5 microg/kg) and inhibition with high doses (2 and 4 microg/ kg) as shown by respective increases and decreases in tumor volume, protein, RNA and amylase contents. In cell cultures, [3H]thymidine incorporation was dose-dependently increased with 10-(10) to 10(-8) M CCK-8 and inhibited with 10(-7) M. Both effects were completely suppressed by the CCK-receptor antagonists CR 1409 and L 364,718 (10(-4) M). Binding studies showed the overexpression of two classes of CCK-A receptors of low and high affinity when compared to the normal pancreas which was less sensitive to CCK-8.


CONCLUSIONS
CCK-8 exerts a biphasic growth response on the acinar pancreatic carcinoma, mediated by two classes of CCK-A receptors overexpressed in the tumour.
Hajri
A
A
Institut de Recherche sur les Cancers de l'Appareil Digestif, Hópitaux Universitaires, Strasbourg, France.
Damgé
C
C
D000818:Animals; D001377:Azaserine / Q000633:toxicity; D018267:Carcinoma, Acinar Cell / Q000139:chemically induced / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D011869:Radioligand Assay; D051381:Rats; D011917:Rats, Inbred Lew; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D007457:Iodine Radioisotopes; D011949:Receptors, Cholecystokinin; D001377:Azaserine; D012844:Sincalide