Abstract: Calorie restriction (CR) inhibits prostate cancer progression, partially through modulation of the IGF axis. IGF-1 receptor (IGF-1R) blockade reduces prostate cancer xenograft growth. We hypothesized that combining calorie restriction with IGF-1R blockade would have an additive effect on prostate cancer growth. Severe combined immunodeficient mice were subcutaneously injected with 22Rv1 cells and randomized to: (1) Ad libitum feeding/intraperitoneal saline (Ad-lib); (2) Ad-lib/20 mg/kg twice weekly, intraperitoneal ganitumab [anti-IGF-1R antibody (Ad-lib/Ab)]; (3) 40% calorie restriction/intraperitoneal saline (CR); (4) CR/ intraperitoneal ganitumab, (CR/Ab). CR and ganitumab treatment were initiated one week after tumor injection. Euthanasia occurred 19 days post treatment. Results showed that CR alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. Ganitumab therapy alone reduced tumor growth but had no effect on final tumor weight. The combination therapy (CR/Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad-lib group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. Tumor AKT activation directly correlated with plasma IGF-1 levels. In conclusion, whereas ganitumab therapy modestly affected 22Rv1 tumor growth, combining IGF-1R blockade with calorie restriction resulted in a significant decrease in final tumor weight and improved metabolic profile.
Keywords: prostate cancer; calorie restriction; IGF-1R blockade
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Galet, C.; Gray, A.; Said, J.W.; Castor, B.; Wan, J.; Beltran, P.J.; Calzone, F.J.; Elashoff, D.; Cohen, P.; Aronson, W.J. Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts. Int. J. Mol. Sci. 2013, 14, 13782-13795.
Galet C, Gray A, Said JW, Castor B, Wan J, Beltran PJ, Calzone FJ, Elashoff D, Cohen P, Aronson WJ. Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts. International Journal of Molecular Sciences. 2013; 14(7):13782-13795.
Galet, Colette; Gray, Ashley; Said, Jonathan W.; Castor, Brandon; Wan, Junxiang; Beltran, Pedro J.; Calzone, Franck J.; Elashoff, David; Cohen, Pinchas; Aronson, William J. 2013. "Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts." Int. J. Mol. Sci. 14, no. 7: 13782-13795.