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

International Journal of Molecular Sciences

Ying-Hsiu Lai¹  Hsin-I Ma²  Yi-Ping Yang²  Chi-Hsien Wang²  Jun-Ming Han²  Dueng-Yuan Hueng²  Shi-Yuan Cheng³  Xiao Xiao⁴  Hao-Ai Shui⁵  Ming-Teh Chen⁶ 

[1] Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan;Department of Neurological Surgery, Tri-Service General Hospital,National Defense Medical Center, Taipei 11490, Taiwan;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;Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan;School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan;

关键词: dsAAV;    decorin;    glioblastoma multiforme;    proteomics;    2-D electrophoresis;   

DOI  :  10.3390/ijms15034393

来源: DOAJ

【 摘 要 】

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 theanti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors.

【 授权许可】

Unknown