Effects of a high-fat diet and L364,718 on growth of human pancreas cancer

Abstract

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.