Skip to main content
Log in

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

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

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, 24th, 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29

    Article  PubMed  Google Scholar 

  2. Sim HG, Cheng CW (2005) Changing demography of prostate cancer in Asia. Eur J Cancer 41:834–845

    Article  PubMed  Google Scholar 

  3. Fleshner N, Bagnell PS, Klotz L, Venkateswaran V (2004) Dietary fat and prostate cancer. J Urol 171:S19–S24

    Article  CAS  PubMed  Google Scholar 

  4. Lophatananon A, Archer J, Easton D et al (2010) Dietary fat and early-onset prostate cancer risk. Br J Nutr 103:1375–1380

    Article  CAS  PubMed  Google Scholar 

  5. Kristal AR, Cohen JH, Qu P, Stanford JL (2002) Associations of energy, fat, calcium, and vitamin D with prostate cancer risk. Cancer Epidemiol Biomarkers Prev 11:719–725

    CAS  PubMed  Google Scholar 

  6. Deneo-Pellegrini H, De Stefani E, Ronco A, Mendilaharsu M (1999) Foods, nutrients and prostate cancer: a case-control study in Uruguay. Br J Cancer 80:591–597

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Andersson SO, Wolk A, Bergstrom R et al (1996) Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden. Int J Cancer 68:716–722

    Article  CAS  PubMed  Google Scholar 

  8. Pollard M, Luckert PH (1985) Promotional effects of testosterone and dietary fat on prostate carcinogenesis in genetically susceptible rats. Prostate 6:1–5

    Article  CAS  PubMed  Google Scholar 

  9. Pollard M, Luckert PH (1986) Promotional effects of testosterone and high fat diet on the development of autochthonous prostate cancer in rats. Cancer Lett 32:223–227

    Article  CAS  PubMed  Google Scholar 

  10. Tamano S, Rehm S, Waalkes MP, Ward JM (1996) High incidence and histogenesis of seminal vesicle adenocarcinoma and lower incidence of prostate carcinomas in the Lobund-Wistar prostate cancer rat model using N-nitrosomethylurea and testosterone. Vet Pathol 33:557–567

    Article  CAS  PubMed  Google Scholar 

  11. Carroll KK, Noble RL (1987) Dietary fat in relation to hormonal induction of mammary and prostatic carcinoma in Nb rats. Carcinogenesis 8:851–853

    Article  CAS  PubMed  Google Scholar 

  12. Pour PM, Groot K, Kazakoff K, Anderson K, Schally AV (1991) Effects of high-fat diet on the patterns of prostatic cancer induced in rats by N-nitrosobis(2-oxopropyl)amine and testosterone. Cancer Res 51:4757–4761

    CAS  PubMed  Google Scholar 

  13. Panchal SK, Poudyal H, Iyer A et al (2011) High-carbohydrate high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57:51–64

    Article  CAS  PubMed  Google Scholar 

  14. Gallou-Kabani C, Vige A, Gross MS et al (2007) C57BL/6 J and A/J mice fed a high-fat diet delineate components of metabolic syndrome. Obesity (Silver Spring) 15:1996–2005

    Article  CAS  Google Scholar 

  15. Ben Sahra I, Laurent K, Loubat A et al (2008) The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 27:3576–3586

    Article  CAS  PubMed  Google Scholar 

  16. Zhou G, Myers R, Li Y et al (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Bodmer WF (2000) Prostate cancer 2000. Prostate Cancer Prostatic Dis 3:218–223

    Article  PubMed  Google Scholar 

  18. Gingrich JR, Greenberg NM (1996) A transgenic mouse prostate cancer model. Toxicol Pathol 24:502–504

    Article  CAS  PubMed  Google Scholar 

  19. Gingrich JR, Barrios RJ, Morton RA et al (1996) Metastatic prostate cancer in a transgenic mouse. Cancer Res 56:4096–4102

    CAS  PubMed  Google Scholar 

  20. Greenberg NM, DeMayo F, Finegold MJ et al (1995) Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 92:3439–3443

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Park SH, Chang SN, Baek MW et al (2013) Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice. Lab Anim Res 29:39–47

    Article  PubMed Central  PubMed  Google Scholar 

  22. Yki-Jarvinen H, K. Nikkila and S Makimattila (1999), Metformin prevents weight gain by reducing dietary intake during insulin therapy in patients with type 2 diabetes mellitus. Drugs 58(Suppl 1): 53–54; discussion 75–82

  23. Wang Y, Corr JG, Thaler HT, Tao Y, Fair WR, Heston WD (1995) Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. J Natl Cancer Inst 87:1456–1462

    Article  CAS  PubMed  Google Scholar 

  24. Saw CL, Wu TY, Paredes-Gonzalez X, Khor TO, Pung D, Kong AN (2011) Pharmacodynamics of fish oil: protective effects against prostate cancer in TRAMP mice fed with a high fat western diet. Asian Pac J Cancer Prev 12:3331–3334

    PubMed  Google Scholar 

  25. Patel P, Abate N (2013) Body fat distribution and insulin resistance. Nutrients 5:2019–2027

    Article  PubMed Central  PubMed  Google Scholar 

  26. Nasteska D, Harada N, Suzuki K, et al. (2014), Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high fat diet condition. Diabetes 63:2332–2343

  27. Kaklamani VG, Linos A, Kaklamani E, Markaki I, Koumantaki Y, Mantzoros CS (1999) Dietary fat and carbohydrates are independently associated with circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 concentrations in healthy adults. J Clin Oncol 17:3291–3298

    CAS  PubMed  Google Scholar 

  28. Freedland SJ, Mavropoulos J, Wang A et al (2008) Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. Prostate 68:11–19

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Venkateswaran V, Haddad AQ, Fleshner NE et al (2007) Association of diet-induced hyperinsulinemia with accelerated growth of prostate cancer (LNCaP) xenografts. J Natl Cancer Inst 99:1793–1800

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

All authors declare there is no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hao-wen Jiang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, H., Hu, Mb., Bai, Pd. et al. Will metformin postpone high-fat diet promotion of TRAMP mouse prostate cancer development and progression?. Int Urol Nephrol 46, 2327–2334 (2014). https://doi.org/10.1007/s11255-014-0823-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-014-0823-x

Keywords

Navigation