| RRC ID |
41598
|
| 著者 |
Yatabe N, Kyo S, Kondo S, Kanaya T, Wang Z, Maida Y, Takakura M, Nakamura M, Tanaka M, Inoue M.
|
| タイトル |
2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
Human telomerase RNA (hTR), an important component of telomerase, is a possible target of telomerase-based cancer gene therapy. The present study was undertaken to assess the efficacy of antisense hTR therapy using newly developed 2-5A (5'-phosphorylated 2'-5'-linked oligoadenylate)-linked oligonucleotides against cervical cancer cells. ME180 and SiHa cells were treated with 2-5A-linked antisense hTR designed to complement the region of hTR between residues 76 and 94. The hTR expression, telomerase activity, cell viability, and apoptosis were then examined. The 2-5A anti-hTR effectively degraded hTR and inhibited telomerase activity. The 2-5A mutant anti-hTR and the anti-hTR without 2-5A were not capable of inhibiting telomerase activity. Inhibition of telomerase by 2-5A anti-hTR rapidly decreased cell viability only in telomerase-positive cells within 3-6 days after the treatment, when telomere length has not yet been shortened. This inhibition was associated with apoptosis, possibly through activation of caspase family members. These findings suggest that 2-5A-linked antisense-hTR therapy has a potent telomerase-inhibitory effect associated with a cytocidal effect from caspase-induced apoptosis, and may therefore be a potential tool in telomerase-based gene therapy against cervical cancers.
|
| 巻・号 |
9(7)
|
| ページ |
624-30
|
| 公開日 |
2002-7-1
|
| DOI |
10.1038/sj.cgt.7700479
|
| PMID |
12082463
|
| MeSH |
Apoptosis*
Blotting, Southern
Cell Survival
Female
Flow Cytometry
Genetic Therapy / methods*
Humans
Oligonucleotides / pharmacology
Oligonucleotides, Antisense / pharmacology*
RNA / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / antagonists & inhibitors*
Telomerase / genetics*
Telomere / metabolism
Time Factors
Transfection
Tumor Cells, Cultured
Uterine Cervical Neoplasms / genetics*
Uterine Cervical Neoplasms / therapy
|
| IF |
4.534
|
| 引用数 |
42
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
ONCOLOGY
GENETICS & HEREDITY
|
| リソース情報 |
| ヒト・動物細胞 |
SUSM-1(RCB0174)
VA-13(RCB0251) |
