Will metformin postpone high-fat diet promotion of TRAMP mouse prostate cancer development and progression?

Int Urol Nephrol. 2014 Dec;46(12):2327-34. doi: 10.1007/s11255-014-0823-x. Epub 2014 Aug 27.

Abstract

Purpose: We aimed to examine the effect of high-fat diet (HFD) on prostate cancer (PCa) development and progression and to investigate whether metformin would postpone PCa development and progression promoted by HFD.

Methods: TRAMP mice were randomly divided into three groups: normal diet group, HFD group and metformin-HFD (Met-HFD) group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24(th), and 28th week, respectively. Serum levels of insulin and IGF-1 were tested by ELISA. Prostate tissue of TRAMP mice was used for HE staining.

Results: A total of 17 deaths of TRAMP mice were observed, including 3 (10 %) from the normal diet group, 10 (33.33 %) from the HFD group, and 4 (13.33 %) from Met-HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P = 0.028), and metformin could moderately decrease the mortality rate by 60.01 % (P = 0.067). Tumor formation rates were not significantly different among the three groups. Levels of glucose, insulin, and IGF-1 tended to increase with TRAMP mice's age in HFD group. TRAMP mice from HFD group had higher serum insulin and IGF-1 levels. A moderate decrease in IGF-1 was also seen in Met-HFD group.

Conclusions: HFD could promote TRAMP mouse PCa development and progression and metformin had moderate effect of reducing PCa mortality rate with a decrease in serum IGF-1 level.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Animals
  • Biomarkers, Tumor / blood
  • Blood Glucose / analysis
  • Diet, High-Fat / adverse effects*
  • Disease Progression
  • Insulin / blood
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Metformin / pharmacology*
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Blood Glucose
  • Insulin
  • Insulin-Like Growth Factor I
  • Metformin