Inwieweit beeinflusst eine dauerhafte enterale Ernährung mit unterschiedlichen Fettsäurekompositionen (n-3, n-6 und n-9) die Inzidenz von Primärtumoren und Lebermetastasen sowie den hepato-pankreatischen Eicosanoidstoffwechsel beim duktalen Pankreaskarzinom?

Abstract

Background: Type and composition of polyunsaturated fatty acids (PUFAs) are suspected to play an important role in carcinogenesis. Thus we investigated the effects of n-3, n-6 and n-9 PUFAs on tumour growth, liver metastasis and concentration of prostaglandins (PG) and leukotrienes (LT) in experimental ductal pancreatic adenocarcinoma. Methods: 90 male hamsters were randomized into 6 groups (Gr.) (n = 15). While Gr. 1–3 were healthy control groups, Gr. 4–6 weekly received subcutaneous injections of 10 mg N-nitrosobis-2-oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1–16 all animals received a standard diet with a raw fat content of 2,9%. In week 17 Gr. 1–6 were allocated to three types of diets: Gr. 1: SHF (= standard high fat diet, rich in n-6 PUFAs)/Gr. 2: FISH-OIL (rich in n-3 PUFAs)/Gr. 3: SMOF (= mixture of n-3, n-6 and n-9 PUFAs)/Gr.4: BOP + SHF/Gr. 5: BOP + SMOF/Gr. 6: BOP + FISH-OIL. After 32 weeks all animals were sacrificed and pancreata as well as livers were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1_α, PGE₂) and leukotrienes were measured. Results: FISH-OIL decreased the number of macroscopically visible pancreatic tumours (Gr. 4–6: 54,5 vs 45,5 vs 9,1%, p < 0,05) as well as the incidence of liver metastases (Gr. 4–6: 90,9 vs 72,7 vs 36,4%, p < 0,05). Furthermore the concentration of PGF1_α, PGE₂ and of leukotrienes were significantly increased in pancreatic carcinomas compared to tumour-free tissue. Moreover levels of PGF1_α and PGE₂ were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of leukotrienes was significantly lower than in non-metastatic hepatic tissue in this group as well as Gr. 4 and Gr. 5. Conclusion: FISHOIL decreased the number of visible pancreatic tumours and the incidenceof histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of leukotrienes compared to extrametastatic hepatic tissue.