801P - IGF-1 related pathways and high-fat diet promotion of TRAMP mouse prostate cancer progression

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Cancer Biology
Prostate Cancer
Basic Scientific Principles
Presenter Hua Xu
Citation Annals of Oncology (2014) 25 (suppl_4): iv255-iv279. 10.1093/annonc/mdu336
Authors H. Xu
  • Urology, Huashan Hospital, Fudan University, 200040 - Shanghai/CN

Abstract

Aim

We aimed to examine the effect of high-fat diet on PCa development and progression by comparing tumor incidence and mortality among TRAMP mice fed with high-fat diet or not, and to investigate the role of IGF-1 related pathway in high-fat diet promotion of TRAMP mouse Pca progression.

Methods

TRAMP mice were randomly divided into two groups: the experimental group - high-fat diet group (n = 42), and the control group - ordinary diet group (n = 42). High-fat diet group TRAMP mice were fed with high-fat forage to induce obesity and insulin resistance. TRAMP mice of both groups were sacrificed and sampled on the 20th, 24th and 28th week respectively. Fasting blood glucose was measured when blood was taken. Serum levels of insulin, IGF-1 and IGF-2 were tested by ELISA. Prostate tissue of TRAMP mice was used for both HE staining and immunohistochemical staining of IGF-1 related pathway proteins, including IGF-1Rα, IGF -1Rß, IGF binding proteins and Akt.

Results

A total of 13 cases of death were observed in the study, including 3 TRAMP mice (7.14%) from the normal diet group, and 10 TRAMP mice (23.81%) from the high-fat diet group. The mortality of TRAMP mice from high-fat diet group was significantly higher than normal diet group (P = 0.035). When TRAMP mice were sacrificed at 20th week, there were 11 TRAMP mice (78.57%) from high-fat diet group had typical PCa, while there were only 5 TRAMP mice (35.71%) from ordinary diet group had typical PCa. The tumor incidence at 20th week of TRAMP mice from high-fat diet group was significantly higher than normal diet group (P = 0.022). Serum IGF-1 level of high-fat diet TRAMP mice was significantly higher than that of normal diet TRAMP mice. The difference was even significant at 28th week with P value of 0.011. In addition, serum IGF-1 level tended to increase with high-fat diet TRAMP mice's age. Immunohistochemical staining of TRAMP mice prostate showed that high-fat diet TRAMP mice had higher positive staining rate of IGF-1Rα, IGF-1Rß, IGFBP3 and Akt than normal diet TRAMP mice. Though other IGF binding proteins were also expressed in TRAMP mice prostate, there was no significant difference of positive staining rate between the two groups.

Conclusions

High-fat diet can promote PCa development and progression. IGF-1 related pathway played an important role in high-fat diet promotion of TRAMP mouse Pca development and progression.

Disclosure

All authors have declared no conflicts of interest.