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

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.

本研究旨在研究针对产生细胞因子的细胞的癌症基因治疗。首先，我们成功建立了产生细胞因子的人类泌尿系癌细胞（包括肾（KU-19-20）和膀胱（KU-19-19））作为靶模型。细胞已被证明可以分泌多种细胞因子，例如粒细胞集落刺激因子（G-CSF）、粒细胞巨噬细胞集落刺激因子（GM-CSF）、白细胞介素-6（IL-6）和然后我们研究了当IκB稳定形式cDNA（已知是NFκB抑制剂）转染到细胞中时，细胞因子产生细胞的细胞生长和凋亡是否可以受到核因子κB（NFκB）的调节。使用腺病毒载体，基因递送显着抑制了这些细胞中多种细胞因子的产生。值得注意的是，基因治疗还观察到细胞凋亡的显着诱导。这些结果表明 NFκB 激活也维持了细胞活力。 as 调节产生细胞因子的癌细胞中细胞因子的产生，因此这些体外实验支持临床前体内研究的基本原理，以证明已建立的肿瘤的生长抑制。

项目成果

Sumitomo M, Tachibana M et al.,: "Overexpression of IL-1ra gene up-regulates interleukin-1beta converting enzyme(ICE) gene expression: possible mechanism underlying IL-1beta-resistance of cancer cells"Br J Cancer. 81:2. 277-86 (1999)

Sumitomo M、Tachibana M 等人：“IL-1ra 基因过度表达上调白细胞介素 1β 转换酶 (ICE) 基因表达：癌细胞 IL-1β 抗性的可能机制”Br J Cancer。

Makoto Sumitomo,Masaaki Tachibana et al: "Induction of apoptosis cytokine-producing bladder cancer cells by adenovirus-mediated IkBa overexpression" Human Gene Therapy. 10. 37-47 (1999)

Makoto Sumitomo、Masaaki Tachibana 等人：“通过腺病毒介导的 IkBa 过度表达诱导产生细胞因子的膀胱癌细胞凋亡”人类基因疗法。

Tachibana M et al: "G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review."Cytokines Cell Mol. Ther. 4:2. 113-20 (1998)

Tachibana M 等人：“人类膀胱癌中 G-CSF 的产生及其促进自分泌生长的能力：综述。”Cytokines Cell Mol。

Tachibana M; Murai M: "G-CSF production in human bladder cancer and its ability to promote autocrine growth: a review."Cytokines Cell Mol Ther. 4:2. 113-120 (1998)

立花M;

M Tachibana et al.: "Autocrine growth promotion by multiple hematopoietic growth factors in the established renal cell carcinoma line(KU-19-20)"Cell&Tissue Research. (in press).

M Tachibana 等人：“多种造血生长因子在已建立的肾细胞癌细胞系 (KU-19-20) 中促进自分泌生长”细胞