Rapid blockade of telomerase activity and tumor cell growth by the DPL lipofection of ribbon antisense to hTR
- Affiliated Author(s)
- 서성일; 장병철; 박종구
- Alternative Author(s)
- Suh, Seong Il; Jang, Byeong Churl; Park, Jong Gu
- Journal Title
- Oncogene
- ISSN
- 0950-9232
- Issued Date
- 2005
- Keyword
- telomerase; hTR; ribbon antisense; DPL transfection
- 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 DNAþPeptideþLipid 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.
Oncogene (2005) 24, 6492–6501. doi:10.1038/sj.onc.1208731;
published online 15 August 2005
Keywords: telomerase; hTR; ribbon antisense; DPL
transfection
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