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

Abstract

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.

• Authors: V Bilim, T Kasahara, H Noboru, K Takahashi, Y Tomita
• Journal: Cancer letters (Cancer Lett) Vol. 155 Issue 2 Pg. 191-8 (Jul 31 2000) ISSN: 0304-3835 [Print] Ireland
• PMID: 10822135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)