Journal of the National Cancer Institute Advance Access originally published online on November 27, 2007
JNCI Journal of the National Cancer Institute 2007 99(23):1793-1800; doi:10.1093/jnci/djm231
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2007. Published by Oxford University Press.
ARTICLES |
Association of Diet-Induced Hyperinsulinemia With Accelerated Growth of Prostate Cancer (LNCaP) Xenografts
Affiliations of authors: Divisions of Urology (VV, AQH, RF, RN, LHK) and Pathology (LMS), Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of Urology, Princess Margaret Hospital, Toronto, ON, Canada (NEF); Departments of Medicine and Oncology, Lady Davis Research Institute, Jewish General Hospital, McGill University, Montreal, Canada (MP)
Correspondence to: Vasundara Venkateswaran, PhD, Division of Urology, S-118B, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N3M5, Canada (e-mail: vasundara.venkateswaran{at}sunnybrook.ca).
Background: Prior research suggested that energy balance and fat intake influence prostate cancer progression, but the influence of dietary carbohydrate on prostate cancer progression has not been well characterized. We hypothesized that hyperinsulinemia resulting from high intake of refined carbohydrates would lead to more rapid growth of tumors in the murine LNCaP xenograft model of prostate cancer.
Methods: Athymic mice were injected subcutaneously with LNCaP human prostate cancer cells and, when tumors were palpable, were randomly assigned (n = 20 per group) to high carbohydrate–high fat or low carbohydrate–high fat diets. Body weight and tumor volume were measured weekly. After 9 weeks, serum levels of insulin and insulin-like growth factor 1 (IGF-1) were measured by enzyme immunoassay. AKT activation and the levels of the insulin receptor in tumor cells were determined by immunoblotting. The in vitro growth response of LNCaP cells to serum from mice in the two treatment groups was measured based on tetrazolium compound reduction. All statistical tests were two-sided.
Results: After 9 weeks on the experimental diets, mice on the high carbohydrate–high fat diet were heavier (mean body weight of mice on the high carbohydrate–high fat diet = 34 g versus 29.1 g on the low carbohydrate–high fat diet, difference = 4.9 g, 95% CI = 3.8 to 6.0 g; P = .003), experienced increased tumor growth (mean tumor volume in mice on high carbohydrate–high fat diet = 1695 versus 980 mm3 on low carbohydrate–high fat diet, difference = 715 mm3, 95% CI = 608 to 822 mm3; P<.001), and experienced a statistically significant increase in serum insulin and IGF-1 levels. Tumors from mice on the high carbohydrate–high fat diet had higher levels of activated AKT and modestly higher insulin receptor levels than tumors from mice on the low carbohydrate–high fat diet. Serum from mice on the high carbohydrate–high fat diet was more mitogenic for LNCaP cells in vitro than serum from mice fed the low carbohydrate–high fat diet.
Conclusion: A diet high in refined carbohydrates is associated with increased tumor growth and with activation of signaling pathways distal to the insulin receptor in a murine model of prostate cancer.
| CONTEXT AND CAVEATS Prior knowledge The influence of diet on prostate cancer progression was not well characterized. Study design Mice carrying human prostate cancer xenografts were randomly assigned to high carbohydrate–high fat and low carbohydrate–high fat diets, and differences in tumor growth and hormone status were recorded. Contribution This study found that a diet high in refined carbohydrates was associated with increased tumor growth and higher levels of insulin and insulin-like growth factor 1. Implications Additional research is needed to determine whether diets associated with reductions in insulin levels may benefit prostate cancer patients. Limitations Mice on the high carbohydrate–high fat diet also consumed less protein, and this may have confounded the associations between carbohydrate intake and cancer growth.
|
Manuscript received March 12, 2007; revised September 15, 2007; accepted October 22, 2007.
Related Article in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 1737.