Cellular and Molecular Life Sciences

, Volume 64, Issue 5, pp 621–631

Evaluation of combination gene therapy with PTEN and antisense hTERT for malignant glioma in vitro and xenografts

Authors

  • Yongping You
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Xiaozeng Geng
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Peng Zhao
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Zhen Fu
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Cunzu Wang
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Shengwu Chao
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Ning Liu
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Ailing Lu
    • Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical University
  • Kevin Gardner
    • Laboratory of Receptor Biology and Gene Expression, Center for Cancer ResearchNational Cancer Institute, National Institutes of Health
  • Peiyu Pu
    • Department of NeurosurgeryTianjin Medical University General Hospital
  • Chunsheng Kong
    • Department of NeurosurgeryTianjin Medical University General Hospital
  • Yun Ge
    • Laboratory of Receptor Biology and Gene Expression, Center for Cancer ResearchNational Cancer Institute, National Institutes of Health
  • Susan I. V. Judge
    • MS Center of Excellence-East, VA Maryland Health Care System, and Department of NeurologyUniversity of Maryland School of Medicine
    • Laboratory of Receptor Biology and Gene Expression, Center for Cancer ResearchNational Cancer Institute, National Institutes of Health
Research Article

DOI: 10.1007/s00018-007-6424-4

Cite this article as:
You, Y., Geng, X., Zhao, P. et al. Cell. Mol. Life Sci. (2007) 64: 621. doi:10.1007/s00018-007-6424-4

Abstract.

Telomerase activation is a critical event in cell immortalization, and an increase in human telomerase reverse transcriptase (hTERT) expression is the key step in activating telomerase. The phosphatase and tensin homolog (PTEN) gene encodes a double-specific phosphatase that induces cell cycle arrest, inhibits cell growth, and causes apoptotic cell death. Here, we evaluated a combined PTEN and antisense hTERT gene therapy for experimental glioma in vitro and in vivo. We demonstrated that infection with antisense-hTERT and wild-type-PTEN adenoviruses significantly inhibited human U251 glioma cell proliferation in vitro and glioma growth in a xenograft mouse model. The efficacy of therapy was obviously higher in the tumor xenografts infected with both PTEN and antisense hTERT than in the gliomas infected with either agent alone at the same total viral dose. Consistent with these results, we showed that telomerase activity and hTERT protein levels were markedly reduced in the glioma cells following adenovirus infection. In contrast, the levels of PTEN protein expression were dramatically increased in these cells. Our data indicate that combination treatment with antisense hTERT and wild-type PTEN effectively suppresses the malignant growth of human glioma cells in vitro and in tumor xenografts, suggesting a promising new approach in glioma gene therapy that warrants further investigation.

Keywords.

Antisense hTERTPTENgliomagene therapycombination therapyxenograft

Copyright information

© Birkhäuser Verlag, Basel 2007