Caspase involved synergistic cytotoxicity of bcl-2 antisense oligonucleotides and adriamycin on transitional cell cancer cells.
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.
Bilim
V
V
Department of Urology, Niigata University School of Medicine, Asahimachi 1, 951-8510, Niigata, Japan.
Kasahara
T
T
Noboru
H
H
Takahashi
K
K
Tomita
Y
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001399:Azure Stains; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D020169:Caspases / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D004789:Enzyme Activation; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008858:Microscopy, Phase-Contrast; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism
D000970:Antineoplastic Agents; D001399:Azure Stains; D016376:Oligonucleotides, Antisense; D004317:Doxorubicin; D020169:Caspases