Inhibitory effects of antisense phosphorothioate oligodeoxynucleotides on pancreatic cancer cell Bxpc-3 telomerase activity and cell growth in vitro

World J Gastroenterol. 2006 Jul 7;12(25):4004-8. doi: 10.3748/wjg.v12.i25.4004.

Abstract

Aim: To investigate the effect of telomerase hTERT gene antisense oligonucleotide (hTERT-ASO) on proliferation and telomerase activity of pancreatic cancer cell line Bxpc-3.

Methods: MTT assay was used to detect the effect of different doses of hTERT-ASO on proliferation of Bxpc-3 cell for different times. To study the anti-tumor activity, the cells were divided into three groups: Control group (pancreatic cancer cell Bxpc-3); antisense oligonucleotide (hTERT-ASO) group; and nosense oligonucleotide group decorated with phosphorothioate. Telomerase activity was detected using TRAP-PCR-ELISA. Cell DNA distribution was examined using flow cytometry assay. Cell apoptosis was observed by transmission electron microscope in each group.

Results: After treatment with 6 mmol/L hTERT-ASO, cell proliferation was inhibited in dose- and time-dependent manner. The telomerase activity decreased after treatment with hTERT-ASO for 72 h. Flow cytometry showed the cell number of G0/G1 phase increased from 2.7% to 14.7%, the cell number of S phase decreased from 72.7% to 51.0%, and a sub-G1 stage cell apoptosis peak appeared in front of G1 stage.

Conclusion: Telomerase antisense oligodeoxy-nucleotide can inhibit the proliferation of pancreatic cancer cell line Bxpc-3 and decrease the telomerase activity and increase cell apoptosis rate in vitro.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Genetic Therapy
  • Humans
  • Oligodeoxyribonucleotides, Antisense / pharmacology*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / pathology*
  • Telomerase / genetics*
  • Telomerase / metabolism*

Substances

  • DNA-Binding Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Telomerase