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
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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.
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. International Journal of Molecular Sciences. 2014; 15(3):4393-4414.
Ma, Hsin-I; Hueng, Dueng-Yuan; Shui, Hao-Ai; Han, Jun-Ming; Wang, Chi-Hsien; Lai, Ying-Hsiu; Cheng, Shi-Yuan; Xiao, Xiao; Chen, Ming-Teh; Yang, Yi-Ping. 2014. "Intratumoral Decorin Gene Delivery by AAV Vector Inhibits Brain Glioblastomas and Prolongs Survival of Animals by Inducing Cell Differentiation." Int. J. Mol. Sci. 15, no. 3: 4393-4414.