Fish oil slows prostate cancer xenograft growth relative to other dietary fats and is associated with decreased mitochondrial and insulin pathway gene expression

Abstract

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 severe combined immunodeficient mice were injected with LAPC-4 human PCa cells. Two weeks following injection, mice were randomized to a Western diet based on fish oil, olive oil, corn oil or animal fat (35% kilocalories from fat). Animals were euthanized when tumor volumes reached 1000 mm(3). Serum was collected at death and assayed for PSA, insulin, insulin-like growth factor-1 (IGF-1), IGF-1-binding protein-3 and prostaglandin E-2 (PGE-2) levels. Tumors were also assayed for PGE-2 and cyclooxygenase-2 levels, and global gene expression was 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 with that in mice consuming diets composed of olive oil, corn oil or animal fat. Although prior studies showed that the amount of fat is important for PCa growth, this study suggests that the type of dietary fat consumed may also be important.

Figure 1

Median Mouse Body Weights by Treatment Arm from the Day of Tumor Inoculation

Figure 2

Median Tumor Volumes by Treatment Arm from the Day of Tumor Inoculation

Figure 3

Kaplan-Meier Survival Curve by Treatment Arm from the Day of Tumor Inoculation – All Diets

Figure 4

Kaplan-Meier Survival Curve by Treatment Arm from the Day of Tumor Inoculation –Fish-oil diet versus other diets combined

Figure 5

Serum IGF-Axis Parameters by Treatment Arm from the Time of Sacrifice 5a. Insulin 5b. IGF-1 5c. IGFBP-3 5d. IGF-1 to IGFBP-3 Ratio

Figure 6

Enrichment Plots of Six Represented Gene Sets Significantly Depleted in Tumors of Fish-Oil-Fed Mice 6a. Schematic of the Molecular Signature Database (MSigDB) 6b. Insulin synthesis and secretion pathways (three gene sets) 6c. Mitochondrial pathways (three gene sets)