Efficient inhibition of human telomerase activity by antisense oligonucle-otides sensitizes cancer c

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:Bomm
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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 of~(60)Co-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 D_0 value.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 D_0 value 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. Aim: To investigate the effect of the antisense otigonucleotides (ASODN) spe-cific 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 . Before and after irradiation of ~ (60) Co-γray, telomerase activity was assayed by telomeric repeat amplification protocol (TRAP-PCR-ELISA), and DNA damage and repair were assayed by the comet assay. The classical colony assay was used to plotthe cell- survival curve, to detect the D_0 value. Results: hTR antisense oligo-nucleotides could downregulate the telomerase activity, increase radiation in-duced DNA damage and reduce the subsequent repair. Future and it could in-hibit the proliferation and decrease the D_0 value which indicates risingradiosensitivity.However, telomere length was unchanged over a short period of time. Confclusion: These findings suggest that an ASODN-based strategy may beused to develop telomeras e inhibitors, which can efficiently sensitize radiotherapy.
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