EFFECTS OF CHOLECYSTOKININ-OCTAPEPTIDE ON A PANCREATIC ACINAR CARCINOMA IN THE RAT

Purpose. To investigate the effects of increasing concentrations of ch olecystokinin octapeptide (CCK-8) on a pancreatic acinar adenocarcinom a. 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. Res ults. CCK-8, administered for 12 successive days, exerted a biphasic a ction on tumour growth: a dose-dependent stimulation with low doses (0 .1 and 0.5 mu g/kg) and inhibition with high doses (2 and 4 mu g/kg) a s shown by respective increases and decreases in tumor volume, protein , RNA and amylase contents. In cell cultures, [H-3]thymidine incorpora tion 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 t he 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 r esponse on the acinar pancreatic carcinoma, mediated by two classes of CCK-A receptors overexpressed in the tumour.