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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

Zhao, Peng; Wang, Cunzu; Fu, Zhen; You, Yongping; Cheng, Yunxiang; Lu, Xiaoming; Lu, Ailin; Liu, Ning; Pu, Peiyu and Kang, Chunsheng, et al. (2007) In International Journal of Oncology 31(2). p.361-368
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
keywords
telomerase activity, glioma, siRNA, hTERT, gene therapy
in
International Journal of Oncology
volume
31
issue
2
pages
361 - 368
publisher
D.A. Spandidos
external identifiers
  • wos:000248286000015
  • scopus:35148876642
ISSN
1019-6439
language
English
LU publication?
yes
id
17001e13-250d-4fd7-9690-c98571dca3e9 (old id 647733)
date added to LUP
2007-12-19 10:44:09
date last changed
2017-01-01 06:36:49
@article{17001e13-250d-4fd7-9690-c98571dca3e9,
  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.},
  author       = {Zhao, Peng and Wang, Cunzu and Fu, Zhen and You, Yongping and Cheng, Yunxiang and Lu, Xiaoming and Lu, Ailin and Liu, Ning and Pu, Peiyu and Kang, Chunsheng and Salford, Leif and Fan, Xiaolong},
  issn         = {1019-6439},
  keyword      = {telomerase activity,glioma,siRNA,hTERT,gene therapy},
  language     = {eng},
  number       = {2},
  pages        = {361--368},
  publisher    = {D.A. Spandidos},
  series       = {International Journal of Oncology},
  title        = {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},
  volume       = {31},
  year         = {2007},
}