Application of antisense human telomerase RNA toward cancer therapy |
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Authors: | K Naka H Yokozaki H Tahara E Tahara |
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Affiliation: | First Department of Pathology, Hiroshima University School of Medicine. |
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Abstract: | We overviewed recent results of anti-tumor effects and inhibition of telomerase activity in tumor cells through antisense human telomerase RNA(hTR). By introducing antisense hTR expression construct into tumor cells, reduction of telomeric DNAs and crisis or cellular senescence occurred in several human cancer cell lines. Antisense oligonucleotides to hTR synthesized with peptide nucleic acids and phosphorothioate deoxyribonucleic acids(PS) also inhibited telomerase activity in vitro. Furthermore, PS antisense hTR had significant effect to decrease tumor size and a number of metastatic nodules in a xenograft human cancer-nude mouse model. Taken together, the telomerase inhibitors targeting to hTR are expected to be novel anti-tumor agents. |
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