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Acta Pharmacol Sin. 2006 Sep;27(9):1185-91. doi: 10.1111/j.1745-7254.2006.00417.x.

Efficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy.

Acta pharmacologica Sinica

Xue-mei Ji, Cong-hua Xie, Ming-hao Fang, Fu-xiang Zhou, Wen-jie Zhang, Ming-sheng Zhang, Yun-feng Zhou

Affiliations

  1. Department of Chemotherapy and Radiation Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.

PMID: 16923339 DOI: 10.1111/j.1745-7254.2006.00417.x

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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