Efficient adenoviral transfer of NF-κB inhibitor sensitizes melanoma to tumor necrosis factor-mediated apoptosis

It has been suggested that the in vitro cytotoxicity of tumor necrosis factor (TNF) toward a number of transformed cell lines could make it a useful agent for anti-tumor therapy. However, many tumor cell lines are resistant to TNF-induced cell death. It has been shown that transcription factors of the NF-κB family, which are themselves activated by TNF, could protect cells against apoptotic cell death. To test whether melanoma cells, which are normally resistant to TNF-mediated killing, can be made susceptible by inhibiting the activation of NF-κB, we generated a recombinant adenovirus expressing a dominant mutant form of IκBα under the control of a CMV promoter. We show here that adenovirus-mediated inhibition of NF-κB function rendered melanoma cells susceptible to the cytotoxic effects of TNF, and thus that NF-κB-inhibiting adenoviruses could become useful adjuvants in TNF- based anti-tumor therapies.