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Int. J. Mol. Sci. 2014, 15(3), 4393-4414; doi:10.3390/ijms15034393
Article

Intratumoral Decorin Gene Delivery by AAV Vector Inhibits Brain Glioblastomas and Prolongs Survival of Animals by Inducing Cell Differentiation

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1 Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan 2 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan 3 Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei 11221, Taiwan 4 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan 5 Department of Neurology, Northwestern Brain Tumor Institute. The Robert H. Lurie Comprehensive Cancer Center, Center of Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA 6 Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA 7 School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan 8 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei 11217, Taiwan 9 Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
* Authors to whom correspondence should be addressed.
Received: 14 November 2013 / Revised: 8 February 2014 / Accepted: 19 February 2014 / Published: 12 March 2014
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

Glioblastoma multiforme (GBM) is the most malignant cancer in the central nervous system with poor clinical prognosis. In this study, we investigated the therapeutic effect of an anti-cancer protein, decorin, by delivering it into a xenograft U87MG glioma tumor in the brain of nude mice through an adeno-associated viral (AAV2) gene delivery system. Decorin expression from the AAV vector in vitro inhibited cultured U87MG cell growth by induction of cell differentiation. Intracranial injection of AAV-decorin vector to the glioma-bearing nude mice in vivo significantly suppressed brain tumor growth and prolonged survival when compared to control non-treated mice bearing the same U87MG tumors. Proteomics analysis on protein expression profiles in the U87MG glioma cells after AAV-mediated decorin gene transfer revealed up- and down-regulation of important proteins. Differentially expressed proteins between control and AAV-decorin-transduced cells were identified through MALDI-TOF MS and database mining. We found that a number of important proteins that are involved in apoptosis, transcription, chemotherapy resistance, mitosis, and fatty acid metabolism have been altered as a result of decorin overexpression. These findings offer valuable insight into the mechanisms of the anti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors.
Keywords: dsAAV; decorin; glioblastoma multiforme; proteomics; 2-D electrophoresis dsAAV; decorin; glioblastoma multiforme; proteomics; 2-D electrophoresis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Ma, H.-I.; Hueng, D.-Y.; Shui, H.-A.; Han, J.-M.; Wang, C.-H.; Lai, Y.-H.; Cheng, S.-Y.; Xiao, X.; Chen, M.-T.; Yang, Y.-P. Intratumoral Decorin Gene Delivery by AAV Vector Inhibits Brain Glioblastomas and Prolongs Survival of Animals by Inducing Cell Differentiation. Int. J. Mol. Sci. 2014, 15, 4393-4414.

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