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Int. J. Mol. Sci. 2013, 14(7), 13782-13795; doi:10.3390/ijms140713782
Article

Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts

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Received: 25 February 2013; in revised form: 22 May 2013 / Accepted: 21 June 2013 / Published: 3 July 2013
(This article belongs to the Special Issue Molecular Research in Urology)
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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 prostate cancer; calorie restriction; IGF-1R blockade
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.


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