Induction of apoptosis against cytokine-producing urological cancer

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This study was designed to investigate cancer gene therapy against cytokine producing cells. Firstable, we succeeded establishment of cytokine producing human urological cancer cells including kidney (KU-19-20) and bladder (KU-19-19) as a target model. These cells have been shown to secrete a variety of cytokines such as granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interleiukin-6 (IL-6) and IL-8. Then we investigated whether the cell growth and apoptosis of cytokine-producing cells can be regulated by nuclear factor kappa B (NFκB). When IκB stable form cDNA (which is known to be the NFκB inhibitor) was transfected into the cells with adenovirus vector, the production of several cytokines was significantly suppressed in these cells by the gene delivery. Notably, the significant induction of apoptosis was also observed by the gene therapy. These results suggest that NFκB 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.