Abstract
We have examined the effects of antisense oligonucleotides to bcl-x on the survival and chemosensitivity of CEM cells, a T-acute lymphoblastic leukemia (T-ALL) cell line. Also, we have measured the levels of Bcl-2, Bcl-x, and Bax in 20 cases of T-ALL. By 18 h after the bcl-x antisense treatment, CEM cells showed over a 75% reduction in the levels of Bcl-xL protein and over 30% decreased viable cell counts compared with cells treated with the control oligonucleotide. The combination of bcl-x antisense plus either dexamethasone or doxorubicin showed either strong synergistic or additive killing of CEM cells, respectively. These findings indicate that bcl-x antisense has cytotoxic activity and increases chemotherapy-induced cell death in CEM cells, a model for T-ALL.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Apoptosis*
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Cell Division / drug effects
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Cells, Cultured
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Dexamethasone / pharmacology*
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Doxorubicin / toxicity*
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Leukemia-Lymphoma, Adult T-Cell / drug therapy*
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Oligodeoxyribonucleotides, Antisense / toxicity*
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins c-bcl-2 / analysis
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Recurrence
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Tumor Cells, Cultured
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bcl-2-Associated X Protein
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bcl-X Protein
Substances
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Antineoplastic Agents
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BAX protein, human
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BCL2L1 protein, human
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Oligodeoxyribonucleotides, Antisense
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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bcl-X Protein
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Dexamethasone
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Doxorubicin