Potentiation of tumor necrosis factor-mediated apoptosis of oral squamous cell carcinoma cells by adenovirus-mediated gene transfer of NF-kappaB inhibitor.
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.
Chen
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Department of Biologic and Materials Science, University of Michigan, Ann Arbor 48109-1078, USA.
Fribley
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A
Wang
C Y
CY
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D003124:Colorimetry; D004789:Enzyme Activation / Q000235:genetics; D004792:Enzyme Precursors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000502:physiology*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
D004792:Enzyme Precursors; D020672:I-kappa B Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases