RT Journal Article SR Electronic T1 Effect of a Low-Fat Diet Combined with IGF-1 Receptor Blockade on 22Rv1 Prostate Cancer Xenografts JF Molecular Cancer Therapeutics JO Mol Cancer Ther FD American Association for Cancer Research SP 1539 OP 1546 DO 10.1158/1535-7163.MCT-11-1003 VO 11 IS 7 A1 Konijeti, Ramdev A1 Koyama, Satomi A1 Gray, Ashley A1 Barnard, R. James A1 Said, Jonathan W. A1 Castor, Brandon A1 Elashoff, David A1 Wan, Junxiang A1 Beltran, Pedro J. A1 Calzone, Frank J. A1 Cohen, Pinchas A1 Galet, Colette A1 Aronson, William J. YR 2012 UL http://mct.aacrjournals.org/content/11/7/1539.abstract AB 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. Mol Cancer Ther; 11(7); 1539–46. ©2012 AACR. This article is featured in Highlights of This Issue, p. 1383