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Updated: May 22, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Effect of a low-fat diet combined with IGF-1 receptor blockade on 22Rv1 prostate cancer xenografts
Ramdev Konijeti1, Satomi Koyama, Ashley Gray
1Department of Urology, School of Medicine, University of California-Los Angeles, Los Angeles, California 90095, USA.
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.
Insights
Combining a low-fat diet with IGF-1R blockade therapy reduced prostate cancer cell proliferation and normalized harmful metabolic markers like insulin and TNF-α, though it did not impact tumor weight.
Area of Science:
- Oncology
- Metabolic Research
- Preclinical Cancer Models
Background:
- Dietary fat reduction and insulin-like growth factor I receptor (IGF-1R) blockade individually inhibit prostate cancer xenograft growth.
- IGF-1R blockade antibody therapy may have untoward metabolic effects.
- Combination therapy may enhance efficacy and mitigate side effects.
Purpose of the Study:
- To investigate the combined effects of a low-fat diet and IGF-1R blockade on prostate cancer growth.
- To assess the impact on metabolic parameters, including serum insulin and TNF-α.
- To evaluate potential additive inhibition of tumor growth and offset adverse metabolic effects.
Main Methods:
- Subcutaneous injection of 22Rv1 prostate cancer cells in immunodeficient mice.
- Randomization into four groups: high-fat diet/saline, high-fat diet/ganitumab, low-fat diet/saline, low-fat diet/ganitumab.
- Measurement of tumor weight, volume, proliferation markers (Ki67), signaling pathway activation (Akt, ERK), and serum metabolic markers (insulin, IGF-I, TNF-α).
Main Results:
- Tumor weights and volumes were not significantly affected by any treatment.
- Low-fat diet combined with IGF-1R blockade (LF/Ab) significantly reduced tumor cell proliferation (Ki67) and ERK activation.
- LF/Ab therapy normalized elevated serum insulin and TNF-α levels observed in other groups, while high-fat diet with antibody (HF/Ab) increased serum insulin.
Conclusions:
- The combination of a low-fat diet and IGF-1R blockade did not yield additive inhibition of prostate cancer tumor weight.
- This combination therapy effectively reduced tumor cell proliferation and ERK activation.
- The combined approach successfully normalized detrimental serum insulin and TNF-α levels, suggesting a beneficial metabolic profile.
