1444 THE EFFECT OF CARBOHYDRATE RESTRICTION ON PROSTATE CANCER TUMOR GROWTH IN A CASTRATE MOUSE XENOGRAFT MODEL (2011)

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111444 THE EFFECT OF CARBOHYDRATE RESTRICTION ON PROSTATE CANCER TUMOR GROWTH IN A CASTRATE MOUSE XENOGRAFT MODEL Jorge Caso, Elizabeth Masko, Jean Thomas, Susan Poulton, Mark Dewhirst, Salvatore Pizzo, and Stephen Freedland Jorge CasoJorge Caso Durham, NC More articles by this author , Elizabeth MaskoElizabeth Masko Durham, NC More articles by this author , Jean ThomasJean Thomas Durham, NC More articles by this author , Susan PoultonSusan Poulton Durham, NC More articles by this author , Mark DewhirstMark Dewhirst Durham, NC More articles by this author , Salvatore PizzoSalvatore Pizzo Durham, NC More articles by this author , and Stephen FreedlandStephen Freedland Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1357AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The role of diet in the development of prostate cancer (PC) is controversial. No- and low-carbohydrate diets delay tumor growth compared to western diet in PC xenograft studies. The effect of these diets in concert with androgen deprivation—from which additional metabolic disturbances are expected—is unknown. We explored this relationship in a mouse xenograft model. METHODS A total of 160 male SCID mice were each injected with 1 × 105 LAPC-4 human PC cells. Of these, 150 mice were castrated and randomized to receive an ad libitum western diet (38 mice, 35% fat, 49% carbohydrates, 16% protein kcals) or fed via a paired-feeding protocol with a no-carbohydrate ketogenic diet (NCKD, 37 mice, 84% fat, 0% carbohydrate, 16% protein kcals), 10% carbohydrate diet (38 mice, 10% carbohydrate, 74% fat, 16% protein kcals), or 20% carbohydrate diet (37 mice, 20% carbohydrate, 64% fat, 16% protein kcals). The remaining 10 mice were not castrated and were fed an ad libitum western diet. Tumor volumes were measured twice a week with calipers. The mice were sacrificed once the volume reached 1,000 mm3 and survival tested among arms using the log-rank test. Serum from the median surviving 8 mice/group was assayed for insulin, IGF-1, and IGFBP-3. RESULTS Caloric intake was tightly regulated with minimal variability in median mouse weights between groups. The 10 non-castrated mice experienced accelerated tumor growth. Among castrated mice, in general, those fed a western diet had the shortest survival while those on a 20% carbohydrate diet had the slowest growth and longest survival (p=0.046, comparing western to 20% carbohydrate). Survival was not significantly different among the various carbohydrate restricted groups (p=0.51). When pooled, there was a trend for improved survival among the carbohydrate restricted diets versus western diet mice (p=0.11). No significant difference in the levels of insulin, IGF-1, and IGFBP-3 was noted among groups at pre-randomization and at sacrifice. CONCLUSIONS No difference in tumor growth, IGF-axis, and survival was found among low- and no-carbohydrate diet groups. A 20% carbohydrate diet, which is equivalent to the maintenance phase of Atkins (and thus achievable in humans) slowed tumor growth vs. a western diet. Though the benefit of carbohydrate restriction was less pronounced than in prior studies in non-castrate mice, these data suggest that diets achievable in humans (e.g. 20% carbohydrate) may play a role in PC management. Human studies are underway. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e579 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jorge Caso Durham, NC More articles by this author Elizabeth Masko Durham, NC More articles by this author Jean Thomas Durham, NC More articles by this author Susan Poulton Durham, NC More articles by this author Mark Dewhirst Durham, NC More articles by this author Salvatore Pizzo Durham, NC More articles by this author Stephen Freedland Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...