A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide
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摘要Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27- mediated antitumor effects, we analyzed the global gene expression profiles of the rAAV-hTERTC27-treated tumor tissues and cell line as compared with that of the control rAAV-green fluorescent protein-treated samples by DNA microarray. Our results suggest that hTERTC27 exerts its effect through complex mechanisms, which involve genes regulating apoptosis, cell adhesion, cell cycle, immune responses, metabolism, signal transduction, transport, transcription and telomere maintenance.
著者Ng SSM, Gao Y, Chau DHW, Li GHY, Lai LH, Huang PT, Huang CF, Huang JJ, Chen YC, Kung HF, Lin MCM
期刊名稱Cancer Gene Therapy
出版年份2007
月份6
日期1
卷號14
期次6
出版社NATURE PUBLISHING GROUP
頁次561 - 572
國際標準期刊號0929-1903
語言英式英語
關鍵詞AAV; glioblastoma; hTERTC27
Web of Science 學科類別Biotechnology & Applied Microbiology; BIOTECHNOLOGY & APPLIED MICROBIOLOGY; Genetics & Heredity; GENETICS & HEREDITY; Medicine, Research & Experimental; MEDICINE, RESEARCH & EXPERIMENTAL; Oncology; ONCOLOGY; Research & Experimental Medicine

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