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

摘要

In pre-clinical models, both dietary fat reduction and IGF-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 SCID mice were injected with 22Rv1 cells subcutaneously. Ten days post-injection, the animals were randomized to four groups: 1) high fat diet + saline (HF), 2) high fat diet + IGF-1R blocking antibody, ganitumab (HF/Ab), 3) low fat diet + saline (LF), and 4) low fat diet + ganitumab (LF/Ab). After nineteen days of treatment, the animals were euthanized, serum was collected and tumors were weighed. Tumor Ki67, Akt and 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-1 receptor 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.