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.

13 Reads
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose. Increasing body mass index (BMI) is associated with higher risk prostate cancer (PC) at presentation. Whether increasing BMI also prompts earlier salvage androgen suppression therapy (sAST) is unknown. Materials and Methods. Between 1995 and 2001, 206 men with unfavorable risk PC were treated with radiation therapy (RT) or RT and six months of androgen suppression therapy in a randomized controlled trial (RCT). 108 sustained PSA failure; 51 received sAST for PSA approaching 10 ng/mL; 49 with BMI data comprised the study cohort. A multivariable Cox regression analysis identified pretreatment factors associated with earlier sAST receipt. Results. Increasing BMI prompted earlier sAST (median years: 3.7 for overweight/obese, 6.9 for normal weight; adjusted hazard ratio (AHR): 1.11; 95% CI: 1.04, 1.18; P = 0.002) as did high versus other risk PC (median: 3.2 versus 5.2 years; AHR: 2.01; 95% CI: 1.05, 3.83; P = 0.03). Increasing median time to sAST was observed for overweight/obese men with high versus other risk PC and for normal-weight men with any risk PC being 2.3, 4.6, and 6.9 years, respectively (P < 0.001 for trend). Conclusion. Increasing BMI was associated with earlier sAST. A RCT evaluating whether BMI reduction delays or eliminates need for sAST is warranted.
    Full-text · Article · Feb 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: A three layer (trilayer) polymeric micelle system based on the self-association of the triblock polymer poly(ethylene glycol)-b-poly{N-[N-(2-aminoethyl)-2-aminoethyl] aspartamide}-b-poly(ɛ-caprolactone) (PEG-b-PAsp(DET)-b-PCL) has been synthesized and investigated for combination delivery of rapamycin (RAP) and siRNA targeting Y-box binding protein-1 (siYB-1). The trilayer micelle is composed of (a) a hydrophilic poly(ethylene glycol) (PEG) block constituting the outer layer to improve pharmacokinetics, (b) an intermediate compartment composed of the cationic poly{2-[(2-aminoethyl)amino] ethyl aspartamide} (PAsp(DET)) segment for interacting with siYB-1, and (c) an inner hydrophobic poly(ɛ-caprolactone) (PCL) compartment for encapsulation of RAP. A major advantage of this system is biocompatibility since PEG and PCL are both approved by the FDA, and PAsp(DET) is a non-toxic pH responsive cationic poly(amino acid)-based polymer. In this study, it has been shown that PCL can encapsulate RAP with high loading efficiencies, and PAsp(DET) can successfully interact with siRNA for efficient transfection/knockdown with negligible cytotoxicity. The enhanced therapeutic efficacy of RAP/siYB-1 micelles was demonstrated in cell cultures and in a PC3 xenograft nude mouse model of human prostate cancer. Herein, we demonstrate that trilayer micelles are a promising approach to improve the simultaneous delivery of combination siRNA/drug therapies.
    No preview · Article · Jun 2013 · Biomaterials
  • Source

    Full-text · Article · Jan 2015
Show more

Similar Publications