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Acta Pharmacologica Sinica 2006 September; 27 (9): 1185-1193; doi: 10.1111/j.1745-7254.2006.00417.x |
| Original Article | [ Full text ] |
| Efficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy |
Xue-mei JI2, Cong-hua XIE2, Ming-hao FANG3, Fu-xiang ZHOU2, Wen-jie ZHANG4, Ming-sheng ZHANG2, Yun-feng ZHOU2,5 2Department of Chemotherapy and Radiation Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China; 3Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; 4Cancer Research Institute, Wuhan University, Wuhan 430071, China |
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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-g 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 D0 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 D0 value which demonstrates rising radiosensitivity. However, telomere length was unchanged over a short period of time.
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Keywords: oligonucleotides,antisense; telomerase; radiotherapy; glioma,astrocytic; gene therapy |
| 1 Project supported by grants from the National Natural Science Foundation of China (No 30171063). |
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