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- Title
Treatment of bladder cancer cells in vitro and in vivo with 2–5A antisense telomerase RNA.
- Authors
Koga, S; Kondo, Y; Komata, T; Kondo, S
- Abstract
Bladder cancer is the most common malignant tumor of the urinary tract. Novel treatment approaches are essential because of the failure of current treatment options to cure a high percentage of patients. Telomerase, a ribonucleoprotein, is detected in almost all bladder cancer, but not in normal bladder tissues. Therefore, telomerase is expected to be a very promising candidate for targeted therapy of bladder cancer. In this study, we synthesized a 19-mer antisense oligonucleotide against the RNA component of human telomerase (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 targeted RNA sequence. Here we demonstrate that treatment with 2-5Aanti-hTR reduced the viability of seven bladder cancer cell lines (UM-UC-2, UM-UC-3, UM-UC-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 Wl38 cells lacking telomerase activity were resistant to the treatment. Furthermore, treatment of subcutaneous UM-UC2 tumors in nude mice with 2-5A-anti-hTR significantly suppressed the tumor growth through induction of apoptosis (P < 0.001). These findings may offer a strong support to the feasibility of the 2-5A-anti-hTR treatment for human bladder cancer.
- Subjects
BLADDER cancer; ANTISENSE RNA
- Publication
Gene Therapy, 2001, Vol 8, Issue 8, p654
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301449