title: Efficient inhibition of human telomerase activity by antisense oligonucleotides sensitizes cancer cells to radiotherapy.
abstract: OBJECTIVE
  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- gamma 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.
  
  
  CONCLUSIONS
  These findings suggest that an ASODN-based strategy may be used to develop telomerase inhibitors, which can efficiently sensitize radiotherapy.
authors.affiliation: Department of Chemotherapy and Radiation Oncology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Ji
authors.forename: Cong-hua
authors.initials: CH
authors.lastname: Xie
authors.forename: Ming-hao
authors.initials: MH
authors.lastname: Fang
authors.forename: Fu-xiang
authors.initials: FX
authors.lastname: Zhou
authors.forename: Wen-jie
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Ming-sheng
authors.initials: MS
authors.lastname: Zhang
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003037:Cobalt Radioisotopes; D004249:DNA Damage; D004260:DNA Repair; D005720:Gamma Rays; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D011836:Radiation Tolerance; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects; D014162:Transfection
chemical_list: D003037:Cobalt Radioisotopes; D016376:Oligonucleotides, Antisense; D019098:Telomerase