Combination therapy of 2-5A antisense against telomerase RNA and cisplatinfor malignant gliomas

Citation
Y. Kondo et al., Combination therapy of 2-5A antisense against telomerase RNA and cisplatinfor malignant gliomas, INT J ONCOL, 18(6), 2001, pp. 1287-1292
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF ONCOLOGY
ISSN journal
1019-6439 → ACNP
Volume
18
Issue
6
Year of publication
2001
Pages
1287 - 1292
Database
ISI
SICI code
1019-6439(200106)18:6<1287:CTO2AA>2.0.ZU;2-Z
Abstract
2',5'-Oligoadenylate (2-5A) linked to an antisense oligonucleotide against human telomerase RNA (2-5A-anti-hTR) is a novel therapeutic modality we hav e recently developed. We designed the oligonucleotide to target telomerase which maintains chromosome integrity in cancer cells. We have already demon strated the efficacy of this new therapy in malignant glioma cells with tel omerase activity. In the present study, we investigated the effect of 2-5A- anti-hTR in combination with cisplatin, an anti-cancer drug commonly used f or malignant glioma patients. Six human malignant glioma cell lines with te lomerase activity were treated with 0.5 muM 2-5A-anti-hTR and/or cisplatin (0, 0.1, 1, 5, 10, or 20 mug/ml) for three days, and cell viability was mea sured using the MTT colorimetric assay. The combination therapy showed syne rgistic effect at 1 mug/ml cisplatin and additive effect at 5 mug/ml cispla tin. TUNEL staining of the treated cells showed significantly increased apo ptotic cells after the combination therapy. Furthermore, tumor growth of su bcutaneous xenografts of human malignant glioma cells in nude mice was effe ctively reduced after the combination therapy for seven. days. Our study sh ows that the tumor-killing effects of the: combined treatments are, at leas t in part, due to induction of apoptosis. 2-5A-anti-hTR is a promising ther apy not only when used alone, but also in combination with cisplatin.