Novel cancer gene therapy using apoptosis-related gene

利用细胞凋亡相关基因的新型癌症基因疗法

• 批准号: 09671304
• 负责人: SHIMIZU Shigeomi
• 金额: $ 2.05万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671304/
• 关键词: caspase-3(CPP32; Yama); Bcl-2; apoptosis; yama; cpp32

Caspase-3 is a member of the cysteine protease family, which plays a crucial role in apoptosis.We applied the human caspase-3 gene as a novel form of anticancer gene therapy.Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, whereas apoptosis was markedly enhanced by the addition of VP-16.In an AH13O liver tumor model, transfection of human caspase-3, but not the empty vector, induced extensive apoptosis and reduced tumor volume, when applied together with VP-16.However, these effect was not observed with a Bcl-2 overexpressing tumor.In conclusion, caspase-3 gene transfection accompanied by an additional death stimulus may be useful anticancer gene therapy, except for Bcl-2 overexpressing tumors.

Caspase-3是半胱氨酸蛋白酶家族的成员，在细胞凋亡中起重要作用。我们将人caspase-3基因作为一种新的抗癌基因治疗形式。单独过表达人caspase-3不能诱导肿瘤细胞凋亡，而加入VP-16可显著促进肿瘤细胞凋亡。在AH 13 O肝癌模型中，转染人caspase-3，而空载体与VP-16联合应用时，可诱导广泛的细胞凋亡和缩小肿瘤体积，但对Bcl-2过表达的肿瘤没有观察到这些作用。

项目成果

S.Shimizu: "Bcl-2 prevents mitochondrial potential loss by regulating ion flux" Proc.Natl.Acad.Sci.USA. 95. 1455-1459 (1998)

S.Shimizu：“Bcl-2 通过调节离子通量来防止线粒体电位损失”Proc.Natl.Acad.Sci.USA。

M.Ohtsu: "Inhibition of apoptosis by an actin-regulatory protein gelsolin" EMBO Journal. 16. 4650-4656 (1997)

M.Ohtsu：“肌动蛋白调节蛋白凝溶胶蛋白抑制细胞凋亡”EMBO 杂志。

S.Shimizu: "Molecular mechanism of apoptosis" Jpn.J.Biochemistry. 70. 14-21 (1998)

S.Shimizu：“细胞凋亡的分子机制”Jpn.J.Biochemistry。

K.Yamabe: "Prevention of hypoxic liver cell necrosis by in vivo human bcl-2 gene transfection." Biochem.Biophys.Res.Commum.243. 217-223 (1998)

K.Yamabe：“通过体内人 bcl-2 基因转染预防缺氧性肝细胞坏死。”

S.Okuno: "Bcl-2 prevents caspase-independent cell death." J.Biol.Chem.273. 34272-34277 (1998)

S.Okuno：“Bcl-2 可以防止不依赖 caspase 的细胞死亡。”