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-2-oxypropylamine (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 (PGF1alpha, 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(1)(alpha), PGE(2) and LT were significantly increased in pancreatic carcinoma compared to tumour-free tissue. Moreover levels of PGF(1)(alpha) 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.
Clinic of Internal Medicine IV, Germany.
I
I
Heukamp
M
M
Kilian
J I
JI
Gregor
C
C
Kiewert
I
I
Schimke
G
G
Kristiansen
M K
MK
Walz
C A
CA
Jacobi
F A
FA
Wenger
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D006224:Cricetinae; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D015237:Dinoprost / Q000737:chemistry / Q000378:metabolism; D015232:Dinoprostone / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D015289:Leukotrienes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011453:Prostaglandins / Q000378:metabolism*
D004042:Dietary Fats, Unsaturated; D005231:Fatty Acids, Unsaturated; D015289:Leukotrienes; D011453:Prostaglandins; D015237:Dinoprost; D015232:Dinoprostone