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

  • Yongping You
  • Xiaozeng Geng
  • Peng Zhao
  • Zhen Fu
  • Cunzu Wang
  • Shengwu Chao
  • Ning Liu
  • Ailing Lu
  • Kevin Gardner
  • Peiyu Pu
  • Chunsheng Kong
  • Yun Ge
  • Susan I. V. Judge
  • Qingdi Q. Li
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

Authors and Affiliations

  • Yongping You
    • 1
  • Xiaozeng Geng
    • 1
  • Peng Zhao
    • 1
  • Zhen Fu
    • 1
  • Cunzu Wang
    • 1
  • Shengwu Chao
    • 1
  • Ning Liu
    • 1
  • Ailing Lu
    • 1
  • Kevin Gardner
    • 2
  • Peiyu Pu
    • 3
  • Chunsheng Kong
    • 3
  • Yun Ge
    • 2
  • Susan I. V. Judge
    • 4
  • Qingdi Q. Li
    • 2
  1. 1.Department of NeurosurgeryFirst Affiliated Hospital of Nanjing Medical UniversityNanjingP. R. China
  2. 2.Laboratory of Receptor Biology and Gene Expression, Center for Cancer ResearchNational Cancer Institute, National Institutes of HealthBethesdaUSA
  3. 3.Department of NeurosurgeryTianjin Medical University General HospitalTianjinP. R. China
  4. 4.MS Center of Excellence-East, VA Maryland Health Care System, and Department of NeurologyUniversity of Maryland School of MedicineBaltimoreUSA