Journal article
Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts
International journal of molecular sciences, Vol.14(7), pp.13782-13795
07/03/2013
DOI: 10.3390/ijms140713782
PMID: 23823800
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.
Details
- Title: Subtitle
- Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts
- Creators
- Colette Galet - University of California, Los AngelesAshley Gray - University of California, Los AngelesJonathan W. Said - University of California, Los AngelesBrandon Castor - University of California, Los AngelesJunxiang Wan - University of Southern CaliforniaPedro J. Beltran - Amgen (United States)Franck J. Calzone - Amgen (United States)David Elashoff - University of California, Los AngelesPinchas Cohen - University of Southern CaliforniaWilliam J. Aronson - University of California, Los Angeles
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.14(7), pp.13782-13795
- DOI
- 10.3390/ijms140713782
- PMID
- 23823800
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Publisher
- MDPI AG
- Number of pages
- 14
- Grant note
- P50CA92131 / National Cancer Institute (NCI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P01AG034906 / Department of Veterans Affairs, NIA; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); US Department of Veterans Affairs 2P30DK063491 / Department of Veterans Affairs, NIDDK P50CA092131 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Wendy and Ken Ruby, President and Secretary of the Ruby Family Foundation
- Language
- English
- Date published
- 07/03/2013
- Academic Unit
- Injury Prevention Research Center; University of Iowa Health Care
- Record Identifier
- 9985138031102771
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