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.
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 pre-established 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.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Cunzu
authors.initials: C
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Fu
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lu
authors.forename: Ailin
authors.initials: A
authors.lastname: Lu
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
authors.forename: Leif G
authors.initials: LG
authors.lastname: Salford
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D019098:Telomerase