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Smith MR , Abubakr Y , Mohammad R , Xie T , Hamdan M , Alkatib A
Antisense Oligodeoxyribonucleotide Down-Regulation of Bcl-2 Gene-Expression Inhibits Growth of the Low-Grade Non-Hodgkins- Lymphoma Cell-Line Wsu-Fsccl
Cancer Gene Therapy. 1995 Sep;2(3) :207-212
AbstractThe BCL-2 gene product is involved in preventing apoptosis. The t(14,18) chromosomal translocation, which results in a fusion messenger RNA containing the entire coding region of BCL-2 and a portion of the immunoglobulin heavy chain gene, is commonly found in follicular lymphoma and appears to play a role in lymphomagenesis by inhibiting cell death. We tested the hypothesis that downregulation of BCL-2 would decrease accumulation of follicular lymphoma cells by treating the t(14,18)-carrying follicular lymphoma cell line WSU-FSCCL in vitro with antisense oligodeoxyribonucleotides (ODNs) directed against BCL-2. We found dose-dependent, sequence-specific inhibition of cell accumulation by an antisense unmodified ODN directed at codons 2 to 7, which downregulated BCL-2 protein levels. This effect was near maximal at an ODN concentration of 40 mu g/mL (6.9 mu mol/L), with minimal toxicity by control sense, reverse, and mutated antisense ODN at the same concentration. The pre-B leukemia cell line REH showed no sequence-specific growth inhibition by the antisense ODN al these concentrations, and BCL-2 protein levels were not altered. These data suggest that WSU-FSCCL may be useful in a murine model to optimize antisense ODN for potential therapeutic utility.
NotesTimes Cited: 23 Article RT282 CANCER GENE THERAPY