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

Makoto Sumitomo, Masaaki Tachibana, Choichiro Ozu, Hirotaka Asakura, Masaru Murai, Masamichi Hayakawa, Hiroshi Nakamura, Atsushi Takayanagi, Nobuyoshi Shimizu

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Abstract

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.

Original languageEnglish
Pages (from-to)37-47
Number of pages11
JournalHuman Gene Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - 1999 Jan 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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    Sumitomo, M., Tachibana, M., Ozu, C., Asakura, H., Murai, M., Hayakawa, M., Nakamura, H., Takayanagi, A., & Shimizu, N. (1999). Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IκBα overexpression. Human Gene Therapy, 10(1), 37-47. https://doi.org/10.1089/10430349950019174