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  • Title: Efficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy.
    Author: Ji XM, Xie CH, Fang MH, Zhou FX, Zhang WJ, Zhang MS, Zhou YF.
    Journal: Acta Pharmacol Sin; 2006 Sep; 27(9):1185-91. PubMed ID: 16923339.
    Abstract:
    AIM: To investigate the effect of the antisense oligonucleotides (ASODN) specific for human telomerase RNA (hTR) on radio sensitization and proliferation inhibition in human neurogliocytoma cells (U251). METHODS: U251 cells were transfected with hTR ASODN or nonspecific oligonucleotides (NSODN). Before and after irradiation of (60)Co- gamma ray, telomerase activity was assayed by telomeric repeat amplification protocol ( TRAP-PCR-ELISA), and DNA damage and repair were examined by the comet assay. The classical colony assay was used to plot the cell-survival curve, to detect the D(0 )value. RESULTS: hTR antisense oligonucleotides could downregulate the telomerase activity, increase radiation induced DNA damage and reduce the subsequent repair. Furthermore, it could inhibit the proliferation and decrease the D(0 ) value which demonstrates rising radiosensitivity. However, telomere length was unchanged over a short period of time. CONCLUSION: These findings suggest that an ASODN-based strategy may be used to develop telomerase inhibitors, which can efficiently sensitize radiotherapy.
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