CHEMOSENSITIZATION OF BLADDER CARCINOMA CELLS BY BCL-xL ANTISENSE OLIGONUCLEOTIDES

Autor: C. A. Stein, Joshua Ojwang, Irina V. Lebedeva, Robert R. Rando, Anthony J. Raffo, Paul A. Cossum
Rok vydání: 2001
Předmět:
Zdroj: Journal of Urology. 166:461-469
ISSN: 1527-3792
0022-5347
DOI: 10.1016/s0022-5347(05)65964-2
Popis: Purpose: We investigated antisense inhibition of anti-apoptotic bcl-xL and bcl-2 proteins to increase chemosensitization in the T24 and 5637 bladder carcinoma cell lines.Materials and Methods: A T24 bladder carcinoma cell line stably over expressing bcl-xL protein was constructed. Apoptosis by cytotoxic agents was estimated by cell cycle analysis and Annexin V binding. To eliminate bcl-xL expression T24 and 5637 cells were treated with C5-propynylated and 2′-O-methylribo-oligonucleotides. Levels of protein and messenger RNA were measured by Western and Northern blot analysis. Cell viability after combined treatment with oligonucleotides and various cytotoxic agents was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and evaluated statistically by Student’s 2-sample t test.Results: Forced over expression of bcl-xL protein desensitized the T24 bladder carcinoma cell line to cytotoxic agents. C5-propynylated and 2′-O-methylribo-oligonucleotides down-regulated bcl-xL protein exp...
Databáze: OpenAIRE