Abstract LB-429: Synergistic effects of low-fat diet combined with IGF-I receptor blockade on 22RV1 prostate cancer xenografts

Abstract

Abstract Introduction: IGF-I receptor (IGF-1R) blockade has previously been shown to slow prostate cancer xenograft growth. Dietary fat reduction also inhibits xenograft growth, possibly by modulation of the IGF axis. We hypothesized that a low-fat (LF) diet combined with IGF-I receptor blockade would cause additive retardation of prostate cancer growth and offset the possible untoward metabolic effects of IGF-1R antibody therapy. Methods: Fifty severe combined immunodeficient mice were injected subcutaneously with 22RV1 cells (suppressible with IGF-1R blockade in vitro) and were randomized to four groups: 1) high-fat (HF) diet with intraperitoneal saline, 2) high-fat diet with intraperitoneal IGF-I receptor blocking antibody from Amgen: AMG479, (HFAb), 3) low-fat diet with intraperitoneal saline (LF), 4) low-fat diet with intraperitoneal AMG479, (LFAb). Treatment with either antibody or saline was initiated 10 days after tumor injection and given twice weekly, tumors were measured serially. The animals were euthanized at 19 days of treatment. Tumors were then weighed and stained for Ki67, TUNEL, and CD31. Serum levels of insulin, resistin, murine IGF-I, murine IGFBP-3, and TNF-alpha were measured. Results: Mean tumor weights were significantly lower (by ∼ 40%) in the HFAb and LFAb group relative to the HF group. There was no difference in mean tumor weight between the HFAb and LFAb groups. Ki67 expression (% positive cells) was significantly decreased in the LFAb group compared to the HFAb group (62 + 29 vs. 94 + 4.3, p<0.001). IGF-1R antibody caused a significant increase in serum insulin levels compared to the LF and HF group, but combining the LF diet with the IGF-1R antibody significantly reduced serum insulin levels by 40% relative to the HFAb group. Likewise, combining a LF diet with the IGF-1R antibody also reduced serum TNF-alpha levels relative to the HF group. Conclusion: IGF-1R antibody therapy inhibited xenograft growth in mice on HF and LF diets. Whereas combining a LF diet with IGF-1R antibody did not have additive growth inhibitory effects on tumor size, there was evidence of decreased tumor cell proliferation, reduced serum insulin levels and reduced pro-inflammatory cytokine levels. Further pre-clinical and clinical trials are warranted to evaluate the role of dietary interventions to enhance anti-tumor effects and offset the metabolic consequences of IGF-1R antibody therapy. Aknowledgements: This work was supported by the NCI grant # P50CA92131 and “The Ruby Family Foundation”. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-429.