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サイトカイン産生腫瘍細胞に対する転写因子(nuclear factor kappa B)抑制による細胞死の誘導：
橘　政昭¹,住友　誠²,村井　勝¹,高柳　淳³,清水信義³ （¹慶大・泌,²防衛医大・泌,³慶大・分生）

ACTIVATION OF THE PROGRAMMED CELL DEATH PATHWAY ON CYTOKINE PRODUCING BLADDER CANCER CELLS BY I-KAPPA-B-ALFA cDNA TRANSFECTION UTILIZED ADENOVIRUS VECTOR:
Masaaki TACHIBANA,¹, Makoto SUMITOMO², Masaru MURAI¹, Atsushi TAKAYANAGI³, Nobuyoshi SHIMIZU (¹ Dept. of Urol., Keio Univ. ² Dept. of Urol., Natl. Defence Med., ³ Dept. of Mol. Med.)

OBJECTIVES: It has been reported that the cytokine production of cancer cells could promote the growth of tumors and thus result in a variety of paraneoplastic syndromes. Nuclear factor kappa B(NF-kB) is one of the transcription factors which regulate cytokine gene expression and it was very recently shown to be a regulatory factor for the induction of apoptosis. In the present study, we determined whether or not the growth and apoptosis of cytokine producing cancer cells can be regulated by NF-kB.MATERIALS AND METHODS: We used the following bladder cancer cell lines; KU19-19, KU-1 and KU-7. KU19-19 was established in our laboratory and produces several cytokines and demonstrates autocrine growth by G-CSF. We established two adenovirus vectors expressing a dominant-negative I-kBα (Adex-I) and lac-Z (Adex-L). The NF-kB DNA binding activity was measured by electrophoretic mobility shift assay(EMSA). Cell survival was measured by an Alamar Blue assay and flow cytometry. The induction of cell death including apoptosis was measured by fragmented DNA ELISA and the TUNEL method. RESULTS: NF-kB was activated in KU19-19 but not in KU-1 and KU-7, respectively. The inhibition of NF-kB activity with adenovirus vectors (multiplicity of infection; moi=20) induced growth inhibition and cell apoptosis on KU19-19, but not on KU-1 and KU-7. In vivo, CONCLUSIONS: These results suggest that the growth of cytokine producing tumors was regulated by NF-kB and therefore the inhibition of NF-kB by adenovirus vector can be used as an effective gene therapy for the treatment of cytokine producing bladder cancer associated paraneoplastic syndromes.