Effects of Cholecystokinin Octapeptide on a Pancreatic Acinar Carcinoma in the Rat

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Abstract

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 μg/kg) and inhibition with high doses (2 and 4 μg/ 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.

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