Abstract
Oral squamous cell carcinoma (SCC) is a malignant tumor which is often resistant to cancer-therapy-mediated apoptosis. The stress-responsive transcription factor nuclear factor kappa B (NF-kappaB), which has been found to be associated with SCC development, plays an essential role in the suppression of tumor necrosis factor (TNF)-mediated apoptosis. Here, we report that an adenovirus-mediated gene transfer of NF-kappaB inhibitor, super-repressor I kappa B alpha (Adv-SR-IkappaBalpha), blocked TNF-induced NF-kappaB activation and sensitized oral SCC cells to TNF killing. Additionally, we found that the inhibition of NFkappaB by Adv-SR-IkappaBalpha enhanced TNF-mediated caspase-8 and -3 activation. These results suggest that NF-kappaB activation is a general mechanism by which oral squamous carcinoma cells are resistant to TNF killing and provide a molecular basis for gene therapy of oral cancer by IkappaBalpha gene transfer in vivo.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Apoptosis / genetics
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Apoptosis / physiology*
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Blotting, Western
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology*
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases / metabolism
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Cell Death / genetics
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Colorimetry
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Enzyme Activation / genetics
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Enzyme Precursors / metabolism
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Enzyme-Linked Immunosorbent Assay
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Gene Transfer Techniques
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Genetic Therapy
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Humans
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I-kappa B Proteins / genetics
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I-kappa B Proteins / physiology*
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Mouth Neoplasms / metabolism
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Mouth Neoplasms / pathology*
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / physiology
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Transduction, Genetic
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Enzyme Precursors
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I-kappa B Proteins
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NF-kappa B
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Tumor Necrosis Factor-alpha
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CASP3 protein, human
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CASP8 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 8
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Caspase 9
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Caspases