Antisense Bcl2 oligonucleotide in cisplatin-resistant bladder cancer cell lines

BJU Int. 2002 Jul;90(1):113-7. doi: 10.1046/j.1464-410x.2002.02799.x.

Abstract

Objective: To determine the change of expression of Bcl2 in cisplatin-resistant bladder cancer cell lines and the reversibility of chemoresistance to cisplatin with antisense oligonucleotide against Bcl2, as higher expression of Bcl2 is associated with drug resistance in many different cancer cell lines.

Materials and methods: In the cisplatin-resistant bladder tumour cell lines T24R1 and T24R2, the expression of Bcl2 was determined by reverse transcription-polymerase chain reaction and Western blot assay, and antisense oligonucleotide targeting of the Bcl2 coding sequence was administered with lipofectin.

Results: The expression of Bcl2 mRNA and protein was greater in T24R1 and T24R2 cells than in the parent T24 cells. Short-term exposure to cisplatin up-regulated Bcl2 mRNA and protein expression in parent T24 cells. Treatment with antisense oligonucleotide down-regulated Bcl2 protein expression and significantly enhanced the cytotoxicity of cisplatin.

Conclusions: Up-regulation of Bcl2 protein expression might be one of the mechanisms of cisplatin resistance in bladder cancer cells, and antisense Bcl2 oligonucleotide may be helpful in chemotherapy for bladder cancer by reversing cisplatin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Blotting, Western
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm
  • Humans
  • Oligonucleotides, Antisense / pharmacology*
  • Phosphatidylethanolamines / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Oligonucleotides, Antisense
  • Phosphatidylethanolamines
  • Proto-Oncogene Proteins c-bcl-2
  • 1,2-dielaidoylphosphatidylethanolamine
  • Cisplatin