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Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer.

Publication ,  Journal Article
Kim, HS; Masko, EM; Poulton, SL; Kennedy, KM; Pizzo, SV; Dewhirst, MW; Freedland, SJ
Published in: BJU Int
October 2012

UNLABELLED: What's known on the subject? and What does the study add? It is known that both lactate inhibition and carbohydrate restriction inhibit tumour growth. What is unknown is whether the two work synergistically together. This study adds that though the combination of lactate inhibition and carbohydrate restriction did not synergistically slow tumour growth in our model, we confirmed that carbohydrate restriction started after tumour inoculation slowed tumour growth. Moreover, lactate inhibition resulted in changes in the tumour microenvironment that may have implications for future metabolic targeting of prostate cancer growth. OBJECTIVE: To determine if a no-carbohydrate ketogenic diet (NCKD) and lactate transporter inhibition can exert a synergistic effect on delaying prostate tumour growth in a xenograft mouse model of human prostate cancer. MATERIALS AND METHODS: 120 nude athymic male mice (aged 6-8 weeks) were injected s.c. in the flank with 1.0 × 10(5) LAPC-4 prostate cancer cells. • Mice were randomized to one of four treatment groups: Western diet (WD, 35% fat, 16% protein, 49% carbohydrate) and vehicle (Veh) treatment; WD and mono-carboxylate transporter-1 (MCT1) inhibition via α-cyano-4-hydroxycinnamate (CHC) delivered through a mini osmotic pump; NCKD (84% fat, 16% protein, 0% carbohydrate) plus Veh; or NCKD and MCT1 inhibition. • Mice were fed and weighed three times per week and feed was adjusted to maintain similar body weights. • Tumour size was measured twice weekly and the combined effect of treatment was tested via Kruskal-Wallis analysis of all four groups. Independent effects of treatment (NCKD vs WD and CHC vs Veh) on tumour volume were tested using linear regression analysis. • All mice were killed on Day 53 (conclusion of pump ejection), and serum and tumour sections were analysed for various markers. Again, combined and independent effects of treatment were tested using Kruskal-Wallis and linear regression analysis, respectively. RESULTS: There were no significant differences in tumour volumes among the four groups (P= 0.09). • When testing the independent effects of treatment, NCKD was significantly associated with lower tumour volumes at the end of the experiment (P= 0.026), while CHC administration was not (P= 0.981). However, CHC was associated with increased necrotic fraction (P < 0.001). CONCLUSIONS: Differences in tumour volumes were observed only in comparisons between mice fed a NCKD and mice fed a WD. • MCT1 inhibition did not have a significant effect on tumour volume, although it was associated with increased necrotic fraction.

Duke Scholars

Published In

BJU Int

DOI

EISSN

1464-410X

Publication Date

October 2012

Volume

110

Issue

7

Start / End Page

1062 / 1069

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Symporters
  • Prostatic Neoplasms
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Neoplasm Transplantation
  • Neoplasm Proteins
  • Necrosis
  • Monocarboxylic Acid Transporters
 

Citation

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Kim, H. S., Masko, E. M., Poulton, S. L., Kennedy, K. M., Pizzo, S. V., Dewhirst, M. W., & Freedland, S. J. (2012). Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int, 110(7), 1062–1069. https://doi.org/10.1111/j.1464-410X.2012.10971.x
Kim, Howard S., Elizabeth M. Masko, Susan L. Poulton, Kelly M. Kennedy, Salvatore V. Pizzo, Mark W. Dewhirst, and Stephen J. Freedland. “Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer.BJU Int 110, no. 7 (October 2012): 1062–69. https://doi.org/10.1111/j.1464-410X.2012.10971.x.
Kim HS, Masko EM, Poulton SL, Kennedy KM, Pizzo SV, Dewhirst MW, et al. Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int. 2012 Oct;110(7):1062–9.
Kim, Howard S., et al. “Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer.BJU Int, vol. 110, no. 7, Oct. 2012, pp. 1062–69. Pubmed, doi:10.1111/j.1464-410X.2012.10971.x.
Kim HS, Masko EM, Poulton SL, Kennedy KM, Pizzo SV, Dewhirst MW, Freedland SJ. Carbohydrate restriction and lactate transporter inhibition in a mouse xenograft model of human prostate cancer. BJU Int. 2012 Oct;110(7):1062–1069.
Journal cover image

Published In

BJU Int

DOI

EISSN

1464-410X

Publication Date

October 2012

Volume

110

Issue

7

Start / End Page

1062 / 1069

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Symporters
  • Prostatic Neoplasms
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Neoplasm Transplantation
  • Neoplasm Proteins
  • Necrosis
  • Monocarboxylic Acid Transporters