Efficient inhibition of human telomerase activity by antisense oligonucle-otides sensitizes cancer cells to radiotherapy

Aim:To investigate the effect of the antisense otigonucleotides(ASODN)spe-cific for human telomerase RNA(hTR)on radio sensitization and proliferationinhibition in human neurogliocytoma cells(U251).Methods:U251 cells weretransfected with hTR ASODN or nonspecific oligonucleotides(NSODN).Beforeand after irradiation of60Co-γray,telomerase activity was assayed by telomericrepeat amplification protocol(TRAP-PCR-ELISA),and DNA damage and repairwere examined by the comet assay.The classical colony assay was used to plotthe cell-survival curve,to detect the D0value.Results:hTR antisense oligo-nucleotides could downregulate the telomerase activity,increase radiation in-duced DNA damage and reduce the subsequent repair.Furthermore,it could in-hibit the proliferation and decrease the D0value which demonstrates risingradiosensitivity.However,telomere length was unchanged over a short period oftime.Conclusion:These findings suggest that an ASODN-based strategy may beused to develop telomerase inhibitors,which can efficiently sensitize radiotherapy.