Impact of polyunsaturated fatty acids on hepato-pancreatic prostaglandin and leukotriene concentration in ductal pancreatic cancer - Is there a correlation to tumour growth and liver metastasis?

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. Ninety male hamsters were randomised into six groups (Gr.) (n = 15). While Gr. 1-3 were healthy control groups, Gr. 4-6 weekly received subcutaneous injections of 10mg N-nitrosobis-2oxypropylamine (BOP)/kg body weight for 12 weeks in order to induce ductal pancreatic adenocarcinoma. Between week 1 and 16 all animals were fed with 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: standard high fat ( = SHF 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 pancreas as well as liver were analysed histologically. Furthermore pancreatic and hepatic concentrations of prostaglandins (PGF1 alpha, PGE(2)) and LT were measured. FISH-OIL decreased number of macroscopically visible pancreatic tumours (Gr. 4-6: 54.5% vs. 45.5% vs. 9.1%, P < 0.05) as well as incidence of liver metastasis (Gr. 4-6: 90.9% vs. 72.7% vs. 36.4%. P < 0.05). Furthermore concentration of PGF(1x), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1x) and PGE(2) were higher in liver metastasis than in extrametastatic hepatic tissue. However, in Gr. 6 (FISH-OIL) intrametastatic concentration of LT was significantly lower than in non-metastatic hepatic tissue as well as in Gr. 4 and Gr. 5. FISH-OIL decreased number of visible pancreatic tumours and incidence of histological proven liver metastasis. This effect might be caused by a decrease of intrametastatic concentration of LT compared to extrametastatic hepatic tissue. (c) 2006 Elsevier Ltd. All rights reserved.