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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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Authors and Affiliations

  1. Institut de Recherche sur les Cancers de 1'Appareil Digestif, Hôpitaux Universitaires, Strasbourg, France

    Amor Hajri

  2. Centre Européen d'Etude du Diabète, Faculté de Médecine, 67000, Strasbourg, France

    Christiane Damgé

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  1. Amor Hajri
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  2. Christiane Damgé
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Hajri, A., Damgé, C. Effects of Cholecystokinin Octapeptide on a Pancreatic Acinar Carcinoma in the Rat. Pharm Res 15, 1767–1774 (1998). https://doi.org/10.1023/A:1011973015634

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