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

作　　者：Xue-mei JI Cong-hua XIE Ming-hao FANG Fu-xiang ZHOU Wen-jie ZHANG Ming-sheng ZHANG Yun-feng ZHOU 

机构地区：[1]Department of Chemotherapy and Radiation Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China [2]Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3]Cancer Research Institute, Wuhan University, Wuhan 430071, China

出　　处：《Acta Pharmacologica Sinica》2006年第9期1185-1191,共7页中国药理学报（英文版）

基　　金：Project supported by grants from the National Natural Science Foundation of China(№30171063).

摘　　要：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 ^60Co-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 Do 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 Do 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.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 ^60Co-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 Do 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 Do 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.

关 键 词：oligonucleotides antisense TELOMERASE RADIOTHERAPY glioma astrocytic gene therapy 

分 类 号：R730.55[医药卫生—肿瘤]