Induction of apoptosis against cytokine-producing urological cancer

诱导细胞凋亡对抗产生细胞因子的泌尿系癌症

• 批准号: 10671493
• 负责人: TACHIBANA Masaaki
• 金额: $ 2.11万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671493/
• 关键词: cytokine-producing cancer cells; NF κ B; gene therapy; adenovirus; IKB; cytokine-producing cancer cells; NF κ B; gene therapy; adenovirus; IKB

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.

这项研究旨在研究针对细胞因子生产细胞的癌症基因治疗。首先，我们成功地建立了肾脏（KU-19-20）和膀胱（KU-19-19）在内的人类泌尿外科细胞的细胞因子，作为靶模型。这些细胞已被证明可以向各种细胞因子进行秘密，例如粒细胞 - 刺激因子（G-CSF），粒细胞巨噬细胞 - 粘液刺激因子（GM-CSF），白介素6（IL-6）（IL-6）和IL-8。然后，我们研究了产生细胞因子细胞的细胞生长和细胞凋亡是否可以由核因子KAPPA B（NFκB）调节。当IκB稳定形式的cDNA（已知为NFκB抑制剂）被转化为具有腺病毒载体的细胞时，基因递送在这些细胞中显着抑制了几种细胞因子的产生。值得注意的是，基因治疗也观察到了凋亡的显着诱导。这些结果表明，NFκB激活保持细胞活力，并调节产生细胞因子的癌细胞中的细胞因子产生，因此这些体外实验支持了临床前体内研究的基本原理，以证明已建立肿瘤的生长抑制。