Treatment of bladder cancer cells in vitro and in vivo with 2-5A antisensetelomerase RNA

Citation
S. Koga et al., Treatment of bladder cancer cells in vitro and in vivo with 2-5A antisensetelomerase RNA, GENE THER, 8(8), 2001, pp. 654-658
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENE THERAPY
ISSN journal
0969-7128 → ACNP
Volume
8
Issue
8
Year of publication
2001
Pages
654 - 658
Database
ISI
SICI code
0969-7128(200104)8:8<654:TOBCCI>2.0.ZU;2-P
Abstract
Bladder cancer is the most common malignant tumor of the urinary tract. Nov el treatment approaches are essential because of the failure of current Tre atment options to cure a high percentage of patients. Telomerase, a ribonuc leoprotein, is detected in almost all bladder cancer, but not in normal bla dder tissues. Therefore. telomerase is expected to be a very promising cand idate for targeted therapy of bladder cancer. In this study, We synthesized a 19-mer antisense oligonucleotide against the RNA component of human telo merase (hTR) linked to a 2-5A molecule (2-5A-anti-hTR) and investigated its antitumor effect against bladder cancer cells. The 2-5A antisense strategy relies on the recruitment and activation of RNase L at the site of targete d RNA sequence. Here we demonstrate that treatment with 2-5A-anti-hTR reduc ed the viability of seven bladder cancer cell lines (UM-UC-2, UM-UC-3, UM-U C-6, UM-UC-9, UM-UC-14,, RT4 and T24) expressing telomerase activity to 21- 55% within 4 days. The cytotoxicity was mainly due to induction of caspase- dependent apoptosis. In contrast, normal fibroblast W138 cells lacking telo merase activity were resistant to the treatment. Furthermore, treatment of subcutaneous UM-UC-2 tumors in nude mice with 2-5A-anti-hTR significantly s uppressed the tumor growth through induction of apoptosis (P < 0.001). Thes e findings may offer a strong support to the feasibility of the 2-5A-anti-h TR treatment for human bladder cancer.