Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression

We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor κB (NF-κB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-κB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-κB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-κB inhibitor IκBα (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 μM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-κB activation stably and strongly. These results suggest that NF-κB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.