Omega-3 fatty acid supplementation reduces tumor growth and vascular endothelial growth factor expression in a model of progressive non-metastasizing malignancy.
BACKGROUND
Omega-3 fatty acids, the principal component of fish oil, have been demonstrated to have antiinflammatory properties. The role of eicosapentaenoic acid (EPA) supplementation for cancer patients is currently under investigation; however, the mechanisms of EPA activity have not been defined. The purpose of this study was to characterize tumor-specific and treatment-specific effects of supplemental dietary EPA in an animal model of progressive malignancy.


METHODS
Fischer 344 rats (200-250 g) underwent flank implantation of the methycholanthrene (MCA)-induced fibrosarcoma on day 0. Rats were randomly divided into 3 treatment groups on day 13: EPA (1 mL, 5.0 g/kg per day) + 10 IU vitamin E; corn oil (1 mL) + 10 IU vitamin E, and saline (1 mL) + 10 IU vitamin E (vitamin E was used to prevent fatty acid oxidation). On day 14, gavage feeding was started and was continued through day 28. The animals were killed on day 29, and the tumors were removed. The tumors were weighed and divided by the tumor-free carcass weight to obtain percentage of tumor volume, and the livers were flash frozen. Vascular endothelial growth factor-alpha (VEGF-alpha) and cyclo-oxygenase 2 (COX-2) mRNA were measured by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
EPA rats had significant reductions in tumor volume compared with isocaloric corn oil and control saline animals (25%, p < .01 and 33%, p < .01, respectively). Rats receiving EPA demonstrated decreased VEGF-alpha mRNA levels (0.023 +/- 0 0.001) compared with those receiving corn oil (0.129 +/- 0.047) or saline (0.150 +/- 0.026; p < .05).


CONCLUSIONS
These data demonstrate that EPA supplementation inhibits tumor growth, potentially through alterations in the expression of the pro-angiogenic VEGF-alpha. The mechanism(s) of EPA as an inhibitor of tumor-related angiogenic growth factors may be associated with COX-2 enzyme fatty acid metabolism and merits further study.
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Department of Surgery, University of Illinois at Chicago, 60612, USA.
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008222:Lymphokines / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015118:Eicosapentaenoic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases