The effects of varying dietary carbohydrate and fat content on survival in a murine LNCaP prostate cancer xenograft model.

Autor:	Mavropoulos JC; Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA., Buschemeyer WC 3rd, Tewari AK, Rokhfeld D, Pollak M, Zhao Y, Febbo PG, Cohen P, Hwang D, Devi G, Demark-Wahnefried W, Westman EC, Peterson BL, Pizzo SV, Freedland SJ
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2009 Jun; Vol. 2 (6), pp. 557-65. Date of Electronic Publication: 2009 May 26.
DOI:	10.1158/1940-6207.CAPR-08-0188
Abstrakt:	Purpose: Numerous dietary factors elevate serum levels of insulin and insulin-like growth factor I (IGF-I), both potent prostate cancer mitogens. We tested whether varying dietary carbohydrate and fat, without energy restriction relative to comparison diets, would slow tumor growth and reduce serum insulin, IGF-I, and other molecular mediators of prostate cancer in a xenograft model. Experimental Design: Individually caged male severe combined immunodeficient mice (n = 130) were randomly assigned to one of three diets (described as percent total calories): very high-fat/no-carbohydrate ketogenic diet (NCKD: 83% fat, 0% carbohydrate, 17% protein), low-fat/high-carbohydrate diet (LFD: 12% fat, 71% carbohydrate, 17% protein), or high-fat/moderate-carbohydrate diet (MCD: 40% fat, 43% carbohydrate, 17% protein). Mice were fed to maintain similar average body weights among groups. Following a preliminary feeding period, mice were injected with 1 x 10(6) LNCaP cells (day 0) and sacrificed when tumors were >or=1,000 mm(3). Results: Two days before tumor injection, median NCKD body weight was 2.4 g (10%) and 2.1 g (8%) greater than the LFD and MCD groups, respectively (P < 0.0001). Diet was significantly associated with overall survival (log-rank P = 0.004). Relative to MCD, survival was significantly prolonged for the LFD (hazard ratio, 0.49; 95% confidence interval, 0.29-0.79; P = 0.004) and NCKD groups (hazard ratio, 0.59; 95% confidence interval, 0.37-0.93; P = 0.02). Median serum insulin, IGF-I, IGF-I/IGF binding protein-1 ratio, and IGF-I/IGF binding protein-3 ratio were significantly reduced in NCKD relative to MCD mice. Phospho-AKT/total AKT ratio and pathways associated with antiapoptosis, inflammation, insulin resistance, and obesity were also significantly reduced in NCKD relative to MCD tumors. Conclusions: These results support further preclinical exploration of carbohydrate restriction in prostate cancer and possibly warrant pilot or feasibility testing in humans.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu