Effect of a low-fat diet combined with IGF-1 receptor blockade on 22Rv1 prostate cancer xenografts.

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-α 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-α 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-α levels.

• Authors: Ramdev Konijeti, Satomi Koyama, Ashley Gray, R James Barnard, Jonathan W Said, Brandon Castor, David Elashoff, Junxiang Wan, Pedro J Beltran, Frank J Calzone, Pinchas Cohen, Colette Galet, William J Aronson
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 11 Issue 7 Pg. 1539-46 (Jul 2012) ISSN: 1538-8514 [Electronic] United States
• PMID: 22562985 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Insulin-Like Growth Factor I
• ganitumab
• Receptor, IGF Type 1
• Extracellular Signal-Regulated MAP Kinases

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacology)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (administration & dosage, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diet, Fat-Restricted
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Male
• Mice
• Mice, SCID
• Prostatic Neoplasms (drug therapy, metabolism)
• Receptor, IGF Type 1 (antagonists & inhibitors)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays