The Effect Of Physical Activity On Tumor Metabolism In The Female Apc/min Mouse

Gastrointestinal cancer is one of the most common forms of cancer and accounts for 35% of cancer related deaths. The APC mutation is found in ~80% of human gastrointestinal cancers. While exercise is known to reduce the incidence and severity of cancer and cancer-related complications, its role as an adjuvant therapy is poorly understood. Research investigating the effect of exercise on gastrointestinal tumor growth and metabolism is critical to unlocking the therapeutic potential of exercise. PURPOSE: To determine the effect of physical activity on tumor metabolism. METHODS: Female ApcMin mice (Apc) underwent a 10-week voluntary wheel run (WR + Apc) physical activity regimen or remained sedentary (SED + Apc). At 15 weeks, tumor tissues were analyzed for metabolite signatures via non-targeted GC/MS metabolomics. RESULTS: Non-targeted metabolomics identified 76 metabolites in the tumors of female ApcMin mice. Eight metabolites were significantly (P < 0.05) increased in WR + Apc mice, and 1 metabolite was significantly (P < 0.05) decreased in WR + Apc mice. Variable Importance in Projection (VIP) analysis also identified cholic acid as a metabolite significantly upregulated in WR + Apc mice. Pathway analysis and enrichment analysis revealed aminoacyl tRNA biosynthesis as a significantly impacted pathway (7 of 48 metabolites) as well as pathways involved in amino acid metabolism. CONCLUSION: These data indicate that physical activity during tumor bearing disrupts altered amino acid and bile acid metabolism and signaling. Cholic acid, a primary bile acid, is known to promote tumorigenesis via upregulated ERK1/2 signaling and inflammation. Interestingly, physical activity appears to downregulate cholic acid and may thus slow tumor growth by inhibiting ERK1/2 signaling and inflammation. Such data may provide valuable insight into understanding how physical activity and exercise may influence tumor metabolism, and the possibility of synergistic effects of anticancer treatments and prescriptive exercise. Furthermore, these data shed important light on the mechanisms of the benefits of exercise in cancer survivors.