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  • Original Paper
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Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR

Abstract

Ribbon antisense (RiAS) to the hTR RNA, a component of the telomerase complex, was employed to inhibit telomerase activity and cancer cell growth. The antisense molecule, hTR-RiAS, combined with enhanced cellular uptake was shown to effectively inhibit telomerase activity and cause rapid cell death in various cancer cell lines. When cancer cells were treated with hTR-RiAS, the level of hTR RNA was reduced by more than 90% accompanied with reduction in telomerase activity. When checked for cancer cell viability, cancer cell lines treated with hTR-RiAS using DNA+Peptide+Lipid complex showed 70–80% growth inhibition in 3 days. The reduced cell viability was due to apoptosis as the percentage of cells exhibiting the sub-G0 arrest and DNA fragmentation increased after antisense treatment. Further, when subcutaneous tumors of a colon cancer cell line (SW480) were treated intratumorally with hTR-RiAS, tumor growth was markedly suppressed with almost total ablation of hTR RNA in the tumor tissue. Cells in the tumor tissue were also found to undergo apoptosis after hTR-RiAS treatment. These results suggest that hTR-RiAS is an effective anticancer reagent, with a potential for broad efficacy to diverse malignant tumors.

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Acknowledgements

This study was supported by generous grants of the CDRC of Korean Science & Engineering Foundation (R13-2002-028-01004-0) and WelGENE Inc., a biotechnology company founded by Dr Jong-Gu Park.

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Correspondence to Jong-Gu Park.

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Bajpai, A., Park, JH., Moon, IJ. et al. Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR. Oncogene 24, 6492–6501 (2005). https://doi.org/10.1038/sj.onc.1208731

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