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.

本研究旨在探讨肿瘤基因治疗对细胞因子产生细胞的影响。首先，我们成功建立了产生肾（KU-19-20）和膀胱（KU-19-19）等人泌尿系统癌细胞的细胞因子作为靶模型。这些细胞已被证明分泌多种细胞因子，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IL-8。研究核因子κB （NFκB）是否能调控细胞因子生成细胞的生长和凋亡。用腺病毒载体转染i - κ b稳定型cDNA（已知为nf - κ b抑制剂）后，这些细胞中几种细胞因子的产生明显受到抑制。值得注意的是，基因治疗还观察到明显的细胞凋亡诱导。这些结果表明，NFκB激活维持细胞活力，并调节细胞因子产生癌细胞的细胞因子产生，因此这些体外实验支持临床前体内研究的基本原理，以证明在已建立的肿瘤中生长抑制。

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