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Journal Article
Research Support, Non-U.S. Gov't
Long-term effects of short hairpin RNA-targeted human telomerase reverse transcriptase on suppression of SGC-7901 cell proliferation by inhibition of telomerase activity.
Oncology Reports 2008 Februrary
Human telomerase reverse transcriptase (hTERT) is an attractive target for cancer gene therapy. However, the poor inhibition of telomerase and a time lag between the inhibition and arrest of cell proliferation limits its use in cancer gene therapy. RNA interference (RNAi) has been proposed as a potential technique for the treatment of cancer with a long-term gene silencing response induced by short hairpin RNA (shRNA). To investigate the long-term effects of telomerase inhibition through the down-regulation of the hTERT gene and the potential role of hTERT in cancer gene therapy, we constructed an shRNA-directed hTERT-expressing vector and introduced it into SGC-7901 cells. A population of cells that stably expressed the shRNA was selected by G418 and continuously cultured in a medium with half the antibiotic concentration for 3 months and the anti-proliferation effects of shRNA-targeted hTERT were then detected. The results showed that shRNA-targeted hTERT significantly inhibited cell proliferation and increased cell apoptosis by down-regulating hTERT expression, thus decreasing telomerase activity. These findings suggest that shRNA-targeted hTERT has long-term anti-proliferation effects on SGC-7901 cells, and it is a potential approach in telomerase-based gene therapy.
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