Lentiviral vector mediated siRNA knock-down of hTERT results in diminished capacity in invasiveness and in vivo growth of human glioma cells in a telomere length-independent manner

Research output: Contribution to journalArticle

Abstract

Glioma cells are characterized by their invasiveness and resistance against conventional therapeutics. Telomerase activity has been suggested to be an important target for glioma treatment. Here we assessed the anticancer effects and its potential mechanisms of lentiviral vector mediated siRNA knock-down of the human telomerase reverse transcriptase (hTERT) in U87MG human glioblastoma cells. Stable expression of anti-hTERT siRNA reduced the hTERT expression and TRAP assay telomerase activity to barely detectable levels. Injection of lentiviral vectors encoding anti-hTERT siRNA significantly inhibited the growth of preestablished macroscopic xenograft tumors, which was in contrast to the finding that no obvious effects on cell growth, cell cycle progression and telomere length were observed in anti-hTERT siRNA expressing U87MG cells during short-term in vitro cultures. The in vivo glioma growth inhibition effect was already evident in the period coincided with no detectable telomere length changes, suggesting that hTERT inhibition may hinder glioma cell growth in a telomere length-independent manner. Importantly, transwell migration assay showed profound inhibitory effect on the invasive capacity of U87MG cells following short-term anti-hTERT siRNA expression. Thus, efficient knock-down of hTERT can inhibit glioma cell proliferation and migration prior to its effect on telomere length.

Details

Authors
  • Peng Zhao
  • Cunzu Wang
  • Zhen Fu
  • Yongping You
  • Yunxiang Cheng
  • Xiaoming Lu
  • Ailin Lu
  • Ning Liu
  • Peiyu Pu
  • Chunsheng Kang
  • Leif Salford
  • Xiaolong Fan
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • telomerase activity, glioma, siRNA, hTERT, gene therapy
Original languageEnglish
Pages (from-to)361-368
JournalInternational Journal of Oncology
Volume31
Issue number2
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes