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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

1
, 1,2
, 2
, 1,3
, 1
, 4
, 5
, 6
, 7,8,*  and 1,9,*
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 Molecular Pathology)
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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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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