Open AccessEfficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy 1
Author(s) -
JI Xuemei,
XIE Conghua,
FANG Minghao,
ZHOU Fuxiang,
ZHANG Wenjie,
ZHANG Mingsheng,
ZHOU Yunfeng
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00417.x
Subject(s) - telomerase , oligonucleotide , radiosensitivity , telomere , microbiology and biotechnology , telomerase reverse transcriptase , transfection , comet assay , cancer research , biology , dna damage , cell culture , dna , chemistry , radiation therapy , medicine , gene , genetics
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‐γ 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.