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

Talitha R. Bakker, Darryl Reed, Toufic Renno, C. Victor Jongeneel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)320-323
Number of pages4
JournalInternational Journal of Cancer
Volume80
Issue number2
DOIs
StatePublished - Jan 18 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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