Role of NF-kappa B and NF-kappa B-regulated Gene Products in Chemoresistance and Radioresistance

Resistance of tumor cells to chemotherapeutic agents and to radiation is one of the major obstacles in the treatment of human cancers. The exact mechanism by which cells develop resistance to chemotherapeutic and radiotherapeutic agents is not well understood. Accumulating evidences over the last decade suggests however that transcription factor nuclear factor-kappa B (NF-kappa B) may play an important role in both chemoresistance and radioresistance. Three lines of evidence support this position. First, most chemotherapeutic agents and gamma radiation activate NF-kappa B in vitro and in vivo. Second, induction of chemoresistance and radioresistance is mediated via genes regulated by NF-kappa B. Third, inhibition of NF-kappa B and NF-kappa B-regulated gene products increases sensitivity of cancer cells to apoptotic action of chemotherapeutic agents and to radiation exposure. This review focuses on current knowledge of the regulation of resistance of tumors cells to chemotherapeutic agents and gamma radiation by NF-kappa B and the therapeutic potential of targeting NF-kappa B in cancer treatment.