Purpose: 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.