Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

ABSTRACT: BACKGROUND:M2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (?-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages. METHODS:MycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300?mm2. To study effects of dietary ?-3 FAs on development of CRPC, ?-3 or ?-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ?-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ?-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay. RESULTS:The ?-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2?±?33.6?mm3) than the ?-6 diet (tumor volume reduction: 148.3?±?35.2; p?=?0.003) and significantly delayed the time to CRPC (p?=?0.006). Likewise, the ?-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p?=?0.003). The ?-3 diet (as compared to the ?-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (?-3). CONCLUSIONS:Dietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC.

SUBMITTER: Liang P 

PROVIDER: S-EPMC7031053 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature