Caspase involved synergistic cytotoxicity of bcl-2 antisense oligonucleotides and adriamycin on transitional cell cancer cells

Cancer Lett. 2000 Jul 31;155(2):191-8. doi: 10.1016/s0304-3835(00)00428-6.


We have previously shown that Bcl-2 expression was negative prognostic factor in transitional cell cancer (TCC), and that TCC cell lines expressing high levels of Bcl-2 are resistant to Adriamycin triggered apoptosis. Here we examined antisense oligonucleotide-mediated downregulation of Bcl-2 expression and its effect on sensitivity to Adriamycin (ADM) treatment in T24 cells. Treatment of T24 cells with 20 microM of bcl-2 antisense phosphorothioate oligodeoxynucleotide (PODN) reduced the Bcl-2 protein level. Combined administration with Adriamycin resulted in synergistic cytotoxicity, accompanied with a 2.4-fold increase in DEVD-specific caspase activity. The finding provides evidence that Bcl-2 expression may be critical for maintaining the drug resistance of TCC. bcl-2 antisense PODN might be useful means for overcoming drug resistance in highly malignant TCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Azure Stains
  • Carcinoma, Transitional Cell / metabolism*
  • Caspases / biosynthesis*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Doxorubicin / pharmacology*
  • Enzyme Activation
  • Genes, bcl-2 / genetics*
  • Humans
  • Immunoblotting
  • In Situ Nick-End Labeling
  • Microscopy, Phase-Contrast
  • Oligonucleotides, Antisense / pharmacology*
  • Time Factors
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / metabolism


  • Antineoplastic Agents
  • Azure Stains
  • Oligonucleotides, Antisense
  • Doxorubicin
  • Caspases