Construction of 6HRE-GFAP-Baxα system specific for glioma gene therapy

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• 作者：Yongji Tian MD (1)
  Guilin Li MD (2)
  Jun Gao MD (2)
  Renzhi Wang MD (2)
  Yanguo Kong MD (2)
  Zhenxing Zhang MD (2)
  Shifang Li MD (2)
  Shiqiang Tian MD (2)
  Wanchen Dou MD (2)
  Bo Zhang MD (2)
  
• 关键词：glioma ; gene therapy ; apoptosis
• 刊名：Frontiers of Medicine
• 出版年：2007
• 出版时间：February 2007
• 年：2007
• 卷：1
• 期：1
• 页码：49-53
• 全文大小：343KB
• 参考文献：1. Komata T, Kondo Y, Kanzawa T, Hirohata S, Koga S, Sumiyoshi H, Srinivasula S M, Barna B P, Germano I M, Takakura M, Inoue M, Alnemn E S, Shay J W, Kyo S, Kondo S. Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter. Cancer Res, 2001, 61(15): 5796-802
  2. Andrae J, Bongcam-Rudloff E, Hansson I, Lendahl U, Westermark B, Nister M. A 1.8kb GFAP-promoter fragment is active in specific regions of the embryonic CNS. Mech Dev, 2001, 107(1-): 181-85 CrossRef
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• 作者单位：Yongji Tian MD (1)
  Guilin Li MD (2)
  Jun Gao MD (2)
  Renzhi Wang MD (2)
  Yanguo Kong MD (2)
  Zhenxing Zhang MD (2)
  Shifang Li MD (2)
  Shiqiang Tian MD (2)
  Wanchen Dou MD (2)
  Bo Zhang MD (2)
  
  1. Department of Neurosurgery, Beijing Tiantan Hospital affiliated China Capital Medical University, Beijing, 100050, China
  2. Department of Neurosurgery, Peking Union Medical College Hospital, Beijing, 100730, China
  

文摘

The aim of this paper is to construct a specific and high-performance gene therapy system for glioma. We constructed a combined promoter 6HRE-GFAP (Hypoxia Responsive Element, Glial Fibrillary Acidic Protein) by gene recombination techniques according to the hypoxia microenvironment in glioma and tested its efficacy and specificity in cultured cells, and then constructed GFAP-Baxα gene expressing system and determined its promoting of apoptosis in glioma cells. Our primary results showed that in U251 and BT325 cell lines, the activity of GFAP promoter was 16.40 and 4.73-fold of the promoter of hTERT (Human Telomerase Reverse Transcriptase), respectively. The activities of 6HRE-GFAP-promoter increased by 3.08 and 1.30-fold under 2% O2sub> condition compared with those under 18% O2sub> condition, while under 0.2% O2sub> condition increased by 8.90 and 2.69-fold, respectively. The glioma cells showed typical apoptotic signs 90 hours after the transient transfection of GFAP-Baxα. In these primary experiments, it showed that 6HRE-GFAP-Baxα system could promote glioma cell apoptosis. It was specific and effective for glioma gene therapy.