Potentiation of Chemotherapeutic Agents following Antagonism of Nuclear Factor kappa B in Human Gliomas

Future success using chemotherapy against human gliomas may result from exploiting unique molecular vulnerabilities of these tumors. Chemotherapy frequently results in DNA damage. When such damage is sensed by the cell, programmed cell death, or apoptosis, may be initiated. However, chemotherapy-induced DNA damage may activate nuclear factor kappa B (NF-κB) and block apoptosis. We inhibited NF-κB using a gene therapy approach to determine whether this would render human glioma cells more susceptible to chemotherapy. U87 and U251 glioma cell lines were infected with either treatment adenovirus containing the gene for a mutant non-degradable form of IκBα, which is an inhibitor of NF-κB nuclear translocation, or empty control virus. Following viral infection, cells were treated either with BCNU, carboplatin, tumor necrosis factor alpha (TNF-α), or SN-38.