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

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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; Kang, Chunsheng; Salford, Leif; Fan, Xiaolong.

I: International Journal of Oncology, Vol. 31, Nr. 2, 2007, s. 361-368.

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Zhao, Peng ; Wang, Cunzu ; Fu, Zhen ; You, Yongping ; Cheng, Yunxiang ; Lu, Xiaoming ; Lu, Ailin ; Liu, Ning ; Pu, Peiyu ; Kang, Chunsheng ; Salford, Leif ; Fan, Xiaolong. / 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. I: International Journal of Oncology. 2007 ; Vol. 31, Nr. 2. s. 361-368.

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TY - JOUR

T1 - 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

AU - Zhao, Peng

AU - Wang, Cunzu

AU - Fu, Zhen

AU - You, Yongping

AU - Cheng, Yunxiang

AU - Lu, Xiaoming

AU - Lu, Ailin

AU - Liu, Ning

AU - Pu, Peiyu

AU - Kang, Chunsheng

AU - Salford, Leif

AU - Fan, Xiaolong

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - telomerase activity

KW - glioma

KW - siRNA

KW - hTERT

KW - gene therapy

M3 - Article

VL - 31

SP - 361

EP - 368

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 2

ER -