Journal article
Effect of a Low-Fat Diet Combined with IGF-1 Receptor Blockade on 22Rv1 Prostate Cancer Xenografts
Molecular cancer therapeutics, Vol.11(7), pp.1539-1546
07/01/2012
DOI: 10.1158/1535-7163.MCT-11-1003
PMID: 22562985
Abstract
In preclinical models, both dietary fat reduction and insulin-like growth factor I receptor (IGF-1R) blockade individually inhibit prostate cancer xenograft growth. We hypothesized that a low-fat diet combined with IGF-1R blockade would cause additive inhibition of prostate cancer growth and offset possible untoward metabolic effects of IGF-1R blockade antibody therapy. Fifty severe combined immunodeficient mice were injected with 22Rv1 cells subcutaneously. Ten days postinjection, the animals were randomized to four groups: (i) high-fat diet + saline (HF); (ii) high-fat diet + IGF-1R blocking antibody, ganitumab (HF/Ab); (iii) low-fat diet + saline (LF); and (iv) low-fat diet + ganitumab (LF/Ab). After 19 days of treatment, the animals were euthanized, serum was collected, and tumors were weighed. Tumor Ki67, Akt and extracellular signal-regulated kinase (ERK) activation, serum insulin, IGF-I and TNF-alpha were measured. In vitro, ganitumab treatment inhibited growth and induced apoptosis in several prostate cancer cell lines. In vivo, tumor weights and volumes were unaffected by the different treatments. The LF/Ab therapy significantly reduced proliferation (Ki67) and ERK activation in tumors. The HF/Ab group had significantly higher serum insulin levels than the HF group. However, LF/Ab combination significantly reduced serum insulin back to normal levels as well as normalizing serum TNF-alpha level. Whereas the combination of low-fat diet and IGF-1R blockade did not have additive inhibitory effects on tumor weight, it led to reduced tumor cell proliferation and a reduction in serum insulin and TNF-alpha levels. Mol Cancer Ther; 11(7); 1539-46. (C)2012 AACR.
Details
- Title: Subtitle
- Effect of a Low-Fat Diet Combined with IGF-1 Receptor Blockade on 22Rv1 Prostate Cancer Xenografts
- Creators
- Ramdev Konijeti - University of California, Los AngelesSatomi Koyama - University of California, Los AngelesAshley Gray - Amgen (United States)R. James Barnard - Amgen (United States)Jonathan W. Said - University of California, Los AngelesBrandon Castor - University of California, Los AngelesDavid Elashoff - University of California, Los AngelesJunxiang Wan - Amgen (United States)Pedro J. Beltran - University of California, Los AngelesFrank J. Calzone - Amgen (United States)Pinchas Cohen - University of California, Los AngelesColette Galet - Amgen (United States)William J. Aronson - Amgen (United States)
- Resource Type
- Journal article
- Publication Details
- Molecular cancer therapeutics, Vol.11(7), pp.1539-1546
- DOI
- 10.1158/1535-7163.MCT-11-1003
- PMID
- 22562985
- NLM abbreviation
- Mol Cancer Ther
- ISSN
- 1535-7163
- eISSN
- 1538-8514
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 8
- Grant note
- P50CA92131 / National Cancer Institute (NCI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P50CA092131 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 2P30DK063491 / National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P01AG034906 / National Institute of Aging (NIA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Ruby Family Foundation
- Language
- English
- Date published
- 07/01/2012
- Academic Unit
- Injury Prevention Research Center; University of Iowa Health Care
- Record Identifier
- 9985137928702771
Metrics
1 Record Views