Long-term effects of short hairpin RNA-targeted human telomerase reverse transcriptase on suppression of SGC-7901 cell proliferation by inhibition of telomerase activity

Xiaobin Qian, Jing Cheng, Aiping Chen, Ying Wang, Yan Tao, Jianping Cao, Zhenqing Feng
Oncology Reports 2008, 19 (2): 575-81
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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