Fish Oil Slows Prostate Cancer Xenograft Growth Relative to Other Dietary Fats and is Associated with Decreased Mitochondrial and Insulin Pathway Gene Expression

BACKGROUND: Previous mouse studies suggest that decreasing dietary fat content can slow prostate cancer (PCa) growth. To our knowledge, no study has yet compared the effect of multiple different fats on PCa progression. We sought to systematically compare the effect of fish oil, olive oil, corn oil, and animal fat on PCa progression. METHODS: A total of 96 male SCID mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were randomized to a fish oil, olive oil, corn oil, or animal fat-based Western diet (35% kcals from fat). Animals were euthanized when tumors reached 1,000mm(3). Serum was collected at sacrifice and assayed for PSA, insulin, IGF-1, IGFBP-3, and PGE-2 levels. Tumors were also assayed for PGE-2 and COX-2 levels and global gene expression analyzed using Affymetrix microarrays. RESULTS: Mice weights and tumor volumes were equivalent across groups at randomization. Overall, fish oil consumption was associated with improved survival, relative to other dietary groups (p=0.014). On gene expression analyses, the fish oil group had decreased signal in pathways related to mitochondrial physiology and insulin synthesis/secretion. CONCLUSIONS: In this xenograft model, we found that consuming a diet in which fish oil was the only fat source slowed tumor growth and improved survival, compared to mice consuming diets composed of olive oil, corn oil, or animal fat. While prior studies showed that the amount of fat is important for PCa growth, the current study suggests that type of dietary fat consumed may also be important.