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The effect of a synthetic analogue of CCK (Thr4,Nle7CCK-9) on growth of SW-1990 human pancreatic cancer was examined in two experimental models. Nude mice bearing SW-1990 pancreatic cancer xenografts were injected with CCK (5, 15, or 25 micrograms/kg) or vehicle twice daily for 20 days. Animals were then sacrificed and tumor volume, weight, protein, and deoxyribonucleic acid (DNA) content were evaluated. SW-1990 cells were grown in vitro and the effects of CCK, secretin, vasoactive intestinal peptide (VIP), and proglumide (a CCK-receptor antagonist) on cell number and DNA synthesis were determined. The highest dose of CCK, 25 micrograms/kg, significantly increased tumor weight, protein content, and DNA content (P less than 0.005). In vitro, CCK caused significant increases in cell counts of up to 47% at six days and 66% at 12 days compared to control. Graded concentrations of CCK had a biphasic effect on DNA synthesis with significant increases of up to 65% (P less than 0.005). CCK-induced cell proliferation was inhibited by proglumide. Secretin slightly increased cancer cell growth, although not as potently as CCK, VIP or secretin in combination with CCK did not show potentiation. These results indicate that growth of some human pancreatic cancers may be influenced by gastrointestinal peptides, of which CCK is the most potent.

The effects of a high-fat diet and the CCK-receptor antagonist, L364,718, were examined on growth of human pancreas cell line SW-1990 xenografted to nude mice. Sixty animals were fed either low-fat (4.3%) or high-fat (20.25%) diet. Fifteen mice in each diet group were treated with L364,718 (2 mg/kg) subcutaneously twice daily for 23 days. On day 24 the animals were sacrificed. Tumor and animal pancreases were dissected and evaluated for weight, protein, and DNA content. When comparing within each diet group, L364,718 significantly decreased tumor volume, weight, protein, and DNA content compared to untreated mice (P less than 0.005). Tumor volume and protein content were significantly larger in untreated animals on the high-fat diet (P less than 0.05) compared to the low-fat diet. Mouse pancreatic weight, protein, and DNA content per kilogram of animal weight were all significantly lower (P less than 0.005) in mice on the low-fat diet treated with L364,718. Pancreatic DNA content was also decreased in both groups of animals on the high-fat diet compared to untreated mice on the low-fat diet. These findings suggest that diets high in unsaturated fat promote the growth of human pancreatic cancer. Since both tumor and pancreas growth are inhibited by the specific CCK-antagonist, L364,718, it is possible that endogenous CCK promotes the growth.

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