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