A high omega-3 fatty acid diet mitigates murine pancreatic precancer development.
J Surg Res. 2009 May 15. PMID: 19631339
BACKGROUND: Diets containing omega-3 (omega-3) fat have been associated with decreased tumor development in the colon, breast, and prostate. We assessed the effects of a diet rich in omega-3 fat on the development of pancreatic precancer in elastase (EL)-Kras transgenic mice and examined the effect of an omega-3 fatty acid on pancreatic cancer cells in vitro. MATERIALS AND METHODS: Two cohorts of EL-Kras mice were fed a high omega-3 fat diet (23% menhaden oil) for 8 and 11 mo and compared with age-matched EL-Kras mice fed standard chow (5% fat). Pancreata from all mice were scored for incidence and frequency of precancerous lesions. Immunohistochemistry was performed for proliferating cell nuclear antigen (PCNA) to assess proliferative index in lesions of mice fed either a high omega-3 or standard diet. In vitro, the effect of the omega-3 fatty acid, docosahexaenoic acid (DHA), on two pancreatic cancer cell lines was assessed. Cancer cell proliferation was assessed with an MTT assay; cell cycle analysis was performed by flow cytometry; and apoptosis was assessed with annexin/PI staining. RESULTS: The incidence, frequency, and proliferative index of pancreatic precancer in EL-Kras mice was reduced in mice fed a high omega-3 fat diet compared with mice fed a standard chow. In vitro, DHA treatment resulted in a concentration-dependent decrease in proliferation through both G1/G0 cell cycle arrest and induction of apoptosis. CONCLUSIONS: A high omega-3 fat diet mitigates pancreatic precancer by inhibition of cellular proliferation through induction of cell cycle arrest and apoptosis.