Effect of intermittent fasting on prostate cancer tumor growth in a mouse model

被引:48
作者
Thomas, J. A., II [1 ]
Antonelli, J. A. [1 ]
Lloyd, J. C. [1 ]
Masko, E. M. [1 ]
Poulton, S. H. [1 ]
Phillips, T. E. [1 ]
Pollak, M. [2 ]
Freedland, S. J. [1 ,3 ,4 ]
机构
[1] Duke Univ, Med Ctr, Dept Surg, Duke Prostate Ctr,Div Urol Surg, Durham, NC 27710 USA
[2] McGill Univ, Dept Oncol, Lady Davis Res Inst, Montreal, PQ, Canada
[3] Durham Vet Adm Hosp, Sect Surg, Durham, NC USA
[4] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
关键词
caloric restriction; diet; IGF-1; fasting; CALORIE RESTRICTION; FACTOR-I; DIETARY RESTRICTION; OXIDATIVE DAMAGE; LIFE-SPAN; BINDING PROTEIN-3; WEIGHT-LOSS; IGF-I; INSULIN; RISK;
D O I
10.1038/pcan.2010.24
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Caloric restriction (CR) has been shown to have anti-cancer properties. However, CR may be difficult to apply in humans secondary to compliance and potentially deleterious effects. An alternative is intermittent CR, or in the extreme case intermittent fasting (IF). In a previous small pilot study, we found 2 days per week of IF with ad libitum feeding on the other days resulted in trends toward prolonged survival of mice bearing prostate cancer xenografts. We sought to confirm these findings in a larger study. A total of 100 (7- to 8-week-old) male severe combined immunodeficiency mice were injected subcutaneously with 1 x 10(5) LAPC-4 prostate cancer cells. Mice were randomized to either ad libitum Western Diet (44% carbohydrates, 40% fat and 16% protein) or ad libitum Western Diet with twice-weekly 24 h fasts (IF). Tumor volumes and mouse bodyweights were measured twice weekly. Mice were killed when tumor volumes reached 1000 mm(3). Serum and tumor were collected for analysis of the insulin/insulin-like growth factor 1 (IGF-1) hormonal axis. Overall, there was no difference in mouse survival (P = 0.37) or tumor volumes (P >= 0.10) between groups. Mouse body weights were similar between arms (P = 0.84). IF mice had significantly higher serum IGF-1 levels and IGF-1/IGFBP-3 ratios at killing (P<0.001). However, no difference was observed in serum insulin, IGFBP-3 or tumor phospho-Akt levels (P >= 0.39). IF did not improve mouse survival nor did it delay prostate tumor growth. This may be secondary to metabolic adaptations to the 24 h fasting periods. Future studies are required to optimize CR for application in humans. Prostate Cancer and Prostatic Diseases (2010) 13, 350-355; doi: 10.1038/pcan.2010.24; published online 24 August 2010
引用
收藏
页码:350 / 355
页数:6
相关论文
共 43 条
  • [11] Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
    Colman, Ricki J.
    Anderson, Rozalyn M.
    Johnson, Sterling C.
    Kastman, Erik K.
    Kosmatka, Kristopher J.
    Beasley, T. Mark
    Allison, David B.
    Cruzen, Christina
    Simmons, Heather A.
    Kemnitz, Joseph W.
    Weindruch, Richard
    [J]. SCIENCE, 2009, 325 (5937) : 201 - 204
  • [12] Dunn SE, 1997, CANCER RES, V57, P4667
  • [13] Transient caloric restriction and cancer risk (The Netherlands)
    Elias, Sjoerd G.
    Peeters, Petra H. M.
    Grobbee, Diederick E.
    van Noord, Paulus A. H.
    [J]. CANCER CAUSES & CONTROL, 2007, 18 (01) : 1 - 5
  • [14] Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans
    Fontana, L
    Meyer, TE
    Klein, S
    Holloszy, JO
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (17) : 6659 - 6663
  • [15] Aging, adiposity, and calorie restriction
    Fontana, Luigi
    Klein, Samuel
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 297 (09): : 986 - 994
  • [16] Modifiable risk factors for colon cancer
    Giovannucci, E
    [J]. GASTROENTEROLOGY CLINICS OF NORTH AMERICA, 2002, 31 (04) : 925 - +
  • [17] Calorie restriction and aging: review of the literature and implications for studies in humans
    Heilbronn, LK
    Ravussin, E
    [J]. AMERICAN JOURNAL OF CLINICAL NUTRITION, 2003, 78 (03) : 361 - 369
  • [18] The anti-carcinogenic effects of dietary restriction: mechanisms and future directions
    Hursting, SD
    Kari, FW
    [J]. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 1999, 443 (1-2) : 235 - 249
  • [19] Hursting SD, 1997, CANCER RES, V57, P2843
  • [20] HURSTING SD, 1993, CANCER RES, V53, P2750