The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model

Division of Urologic Surgery, Duke Prostate Center, Department of Surgery, Duke University Medical Center, Durham, North Carolina.
The Prostate (Impact Factor: 3.57). 04/2011; 73(5). DOI: 10.1002/pros.22586
Source: PubMed


No- and low-carbohydrate diets delay tumor growth compared to western diet (WD) in prostate cancer (PCa) xenograft studies. The effect of these diets in concert with androgen deprivation is unknown.

A total of 160 male SCID mice were injected with 1× 10(5) LAPC-4 human PCa cells. Of these, 150 mice were castrated and randomized to an ad libitum WD or fed via a paired-feeding protocol with a no-carbohydrate ketogenic diet (NCKD), 10% carbohydrate diet, or 20% carbohydrate diet. The remaining 10 mice were not castrated and were fed an ad libitum WD. The mice were sacrificed once volumes reached 1,000 mm3 and survival tested using the log-rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF-1, and IGFBP-3.

Body weights were roughly equal among groups. The 10 non-castrated mice experienced accelerated tumor growth. Among castrated mice, WD had the most rapid tumor growth; 20% carbohydrate diet the slowest (P = 0.046). Survival was not significantly different among the various carbohydrate restricted groups (P = 0.51). When pooled, there was a non-significant trend (P = 0.11) in improved survival among the carbohydrate restricted diets versus WD. No significant difference in serum insulin, IGF-1, and IGFBP-3 levels was noted among all groups at pre-randomization or at sacrifice.

A 20% carbohydrate diet slowed tumor growth versus a WD. Though the benefit of carbohydrate restriction was somewhat less than in prior studies in non-castrate mice, these data still suggest diets achievable in humans may play a role in PCa management.

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    • "Higher body mass index (BMI) has been shown in multiple studies of men with PC being associated with increased PC-specific mortality [4] [5], increased risk of PSA failure following radical prostatectomy [6] [7] or external beam radiation therapy (RT) [8] [9], higher risk disease at presentation [10] [11] [12], and higher likelihood of castrate-resistant disease or metastases following androgen suppression therapy (AST) [13], after adjusting for known risk factors. Possible explanations for why increased BMI could promote more aggressive disease [14] include diet-induced hyperinsulinemia leading to tumor growth [5] [15] [16], increased estradiol and low testosterone serum concentrations in obese men producing more aggressive, testosterone independent PC, since such cancers would have arisen in an environment where testosterone was low [17] [18], chronic subclinical inflammation [19], or functional single nucleotide polymorphisms [20]. "
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    Biomaterials 06/2013; 34(28). DOI:10.1016/j.biomaterials.2013.05.010 · 8.56 Impact Factor
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    Frontiers in Endocrinology 05/2015; 6:77. DOI:10.3389/fendo.2015.00077
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