Skip to main content
Log in

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

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

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<0.005). Tumor volume and protein content were significantly larger in untreated animals on the high-fat diet (P<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<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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Norell SE, Ahlbom A, Erwald R, Jacobson G, Lindberg-Navier I, Olin R, Tornberg B, Wiechel KL: Diet and pancreatic cancer: A case-control study. Am J Epidemiol 124:894–902, 1986

    Google Scholar 

  2. Hopkins GJ, West CE: Possible roles of dietary fats in carcinogenesis. Life Sci 19:1103–1116, 1976

    Google Scholar 

  3. Berg JW: Can nutrition explain the pattern of international epidemiology of hormone-dependent cancers? Cancer Res 35:3345–3350, 1975

    Google Scholar 

  4. Roebuck BD, Yager JD, Longnecker DS: Dietary promotion of azaserine-induced pancreatic carcinogenesis. Proc Am Assoc Cancer Res 21:109, 1980 (abstract)

    Google Scholar 

  5. Roebuck BD, Yager JD, Longnecker DS, Wilpone SA: Promotion by unsaturated fat of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res 41:3961–3966, 1981

    Google Scholar 

  6. Birt DF, Salmasi S, Pour PM: Enhancement of experimental pancreatic cancer in Syrian golden hamsters by dietary fat. J Natl Cancer Inst 67:1327–1332, 1981

    Google Scholar 

  7. Roebuck BD, Yager JD, Longnecker DS: Dietary modulation of azaserineinduced pancreatic carcinogenesis in the rat. Cancer Res 41:888–893, 1981

    Google Scholar 

  8. O'Connor TP, Roebuck BD, Peterson F, Campbell TC: Effect of dietary intake of fish oil and fish protein on the development ofl-azaserine-induced preneoplastic lesions in the rat pancreas. J Natl Cancer Inst 75:959–962, 1985

    Google Scholar 

  9. Fried GM, Ogden WD, Greeley G, Thompson JC: Correlation of release and actions of cholecystokinin in dogs before and after vagotomy. Surgery 93:786–791, 1983

    Google Scholar 

  10. Meyer J, Jones R: Canine pancreatic responses to intestinally perfused fat and products of fat digestion. Am J Physiol 226:1178–1187, 1974

    Google Scholar 

  11. Jansen JBMJ, Lambers CBHW: Molecular forms of cholecystokinin in plasma from normal and gastrectomized human subjects following a fat meal. Peptides 8:801–805, 1987

    Google Scholar 

  12. Longnecker DS, Lhoste EF, Roebuck BD: Enhancement of growth and conversion of pheonotype in azaserine-induced acinar cell foci of rats fed FOY-305. Fed Proc 46:586, 1987 (abstract)

    Google Scholar 

  13. McGuiness EE, Morgan RCH, Levison DA, Hopwood D, Wormsley KG: Interaction of azaserine and raw soya flour on the rat pancreas. Scand J Gastroenterol 16:49–56, 1981

    Google Scholar 

  14. Howatson AG, Carter DC: Pancreatic carcinogenesis-enhancement by cholecystokinin in the hamster-nitrosamine model. Br J Cancer 51:107–114, 1985

    Google Scholar 

  15. Johnson FE, LaRegina MC, Martin SA, Bashiti HM: Cholecystokinin inhibits pancreatic and hepatic carcinogenesis. Cancer Det Prev 6:389–401, 1983

    Google Scholar 

  16. Andren-Sandberg A, Dawiskiba S, Ihse I: Studies of the effects of cerulein administration on experimental pancreatic carcinogenesis. Scand J Gastroenterol 19:122–128, 1984

    Google Scholar 

  17. Smith JP, Mohesky C, Barrett B, Solomon TE: CCK stimulates growth of human pancreatic cancer. Dig Dis Sci 31:1150, 1986 (abstract)

    Google Scholar 

  18. Smith JP, Barrett B, Solomon TE: CCK stimulates growth of five-human pancreatic cancers in serum-free medium. Gastroenterology 92:1646, 1987 (abstract)

    Google Scholar 

  19. Maani R, Townsend CM, Gomez G, Thompson JC, Singh P: A potent CCK receptor antagonist (L364, 718) inhibits growth of human pancreatic cancer in nude mice. Gastroenterology 94:A274, 1988 (abstract)

    Google Scholar 

  20. Douglas BR, Woutersen RA, Jansen JGMJ, DeJong AJL, Rovati LC, Lamers CBHW: Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesis on azaserine-induced lesions in rat pancreas. Gastroenterology 96:462–469, 1989

    Google Scholar 

  21. Kyriazis AP, McCombs III WB, Sandberg AA, Kyriazis AA, Sloane NH, Lepera R: Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse. Cancer Res 43:4393–4401, 1983

    Google Scholar 

  22. Osieka R, Houchens DP, Goldin A, Johnson RK: Chemotherapy of human colon cancer xenografts in athymic nude mice. Cancer 40:2640–2650, 1977

    Google Scholar 

  23. Lowry OH, Rosebrough NJ, Farr AL, Randall RS: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951

    Google Scholar 

  24. Burton K: A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:315–323, 1956

    Google Scholar 

  25. Tannenbaum A: The genesis and growth of tumors: Ill effects of a high-fat diet. Cancer Res 2:468–475, 1942

    Google Scholar 

  26. Carroll KK, Braden LM, Bell JA, Kalamegham R: Fat and cancer. Cancer 58:1818–1825, 1986

    Google Scholar 

  27. Carroll KK, Hopkins GJ: Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis. Lipids 14:155–158, 1979

    Google Scholar 

  28. Stemmermann GN, Nomura AM, Heilbrun L: Dietary fat and the risk of colorectal cancer. Cancer Res 44:4633–4677, 1984

    Google Scholar 

  29. Reddy BS, Maeura Y: Tumor promotion by dietary fat in azoxymethane-induced colon carcinogenesis in female F344 rats: Influence of amount and source of dietary fat. J Natl Cancer Inst 72:745–750, 1984

    Google Scholar 

  30. Reddy BS: Influence of dietary fat, protein, and fiber on colon cancer development.In: Animal Products in Human Nutrition. DC Beitz, RG Hanson (eds). New York, Academic Press, 1982, pp 437–460.

    Google Scholar 

  31. Reddy BS, Tanaka T, Simi B: Effect of different levels of dietary trans fat or corn oil on azoxymethane-induced colon carcinogenesis in F344 rats. J Natl Cancer Inst 75:791–798, 1985

    Google Scholar 

  32. Rodriquez PM, Cruz NI, Gonzalez CI, Lopez R: The effect of a high fat diet on the incidence of colonic cancer after cholecystectomy in mice. Cancer 62:727–729, 1988

    Google Scholar 

  33. Minoura T, Toshiyaki T, Sakaguchi M, Takada H, Yamamura M, Hioki K, Yamamoto M: Effect of dietary eicosapentaenoic acid on azoxymethane-induced colon carcinogenesis in rats. Cancer Res 48:4790–4794, 1988

    Google Scholar 

  34. Carter CA, Milholland RJ, Shea W, Ip MM: Effect of prostaglandin synthetase inhibitor indomethacin on 7, 12-dimethylbenz[a]-anthrancene-induced mammary tumorigenesis in rats fed different levels of fat. Cancer Res 43:3559–3562, 1983

    Google Scholar 

  35. Reddy BS, Maruyama H: Effect of dietary fish oil on azoxymethane-induced colon carcinogenesis in male F344 rats. Cancer Res 46:3367–3370, 1986

    Google Scholar 

  36. Silver JA, Flood JF, Song AM, Morley JE: Evidence for a physiological role for CCK in the regulation of food intake in mice. Am J Physiol 256:R646-R652, 1989

    Google Scholar 

  37. Reddy BS, Chung-Xiou W, Maruyama H: Effect of restricted caloric intake on azoxymethane-induced colon tumor incidence in male F344 rats. Cancer Res 47:1226–1228, 1987

    Google Scholar 

  38. Chang RSL, Lotti VJ, Chen TB, Kunkel KA: Characterization of the binding of [3H]-±L364,718: A new potent, nonpeptide cholecystokinin antagonist radioligand selective for peripheral receptors. Mol Pharmacol 30:212–217, 1986

    Google Scholar 

  39. Louie DS, Liang JP, Owyang C: Characterization of a new CCK antagonist, L364,718in vitro andin vivo studies. Am J Physiol 255:G261-G266, 1988

    Google Scholar 

  40. Walsh JH: Gastrointestinal hormones.In: Physiology of the Gastrointestinal Tract. LR Johnson (ed). New York, Raven Press, 1987, pp 181–253

    Google Scholar 

  41. Jacobs LR: Effect of short-term dietary fat on cell growth in rat gastrointestinal mucosa and pancreas. Am J Clin Nutr 37:361–367, 1983

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by grant IN-109L from the American Cancer Society, grant CA50303-01 from the National Institutes of Health, and by the research services of the Veterans Administration.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, J.P., Kramer, S. & Bagheri, S. Effects of a high-fat diet and L364,718 on growth of human pancreas cancer. Digest Dis Sci 35, 726–732 (1990). https://doi.org/10.1007/BF01540175

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01540175

Key words

Navigation