Development of a novel approach to hepatocellular carcinoma

开发治疗肝细胞癌的新方法

• 批准号: 08670616
• 负责人: MANO Hiroyuki
• 金额: $ 1.41万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670616/
• 关键词: hepatocellular carcinoma; alpha fetoprotein; 自殺遺伝子; アルファフェトプロティン

We have currently only a few ways to treat hepatocellular carcinoma (HCC). To develop a novel approach to treat HCC,we have here investigated whether the promoter of alpha feto-protein (AFP) gene can confer a tumor-specific expression of the cytosine deaminase (CD) gene. The AFP promoter fragment of 1.2 kbp was ligated with the CD cDNA or the reporter luciferase cDNA.These expression cassettes were subcloned into a retroviral vector plasmid, pLNSX,and were used to generate recombinant retroviruses.Infection of AFP-luciferase retrovirus resulted in the AFP-producing cell-specific expression of luciferase. Furthermore, addition fo 5'-fluorocytosine into the culture media induced apoptosis only in the AFP-producing HCC cell lines, but not in 3T3 or Hela cells. Taken together, our data prove that the AFP-promoter can become a useful tool to confer tumor-specific suicide in HCC cells.

我们目前只有几种方法来治疗肝细胞癌（HCC）。为了开发一种新的治疗肝癌的方法，我们在这里研究了甲胎蛋白（AFP）基因的启动子是否可以赋予胞嘧啶脱氨酶（CD）基因的肿瘤特异性表达。将1.2kbp的AFP启动子片段与CD cDNA或报告基因荧光素酶cDNA连接，亚克隆到逆转录病毒载体pLNSX中，构建重组逆转录病毒，感染AFP荧光素酶逆转录病毒，使AFP荧光素酶在AFP产生细胞中特异性表达。此外，向培养基中添加5 '-氟胞嘧啶仅在产生AFP的HCC细胞系中诱导凋亡，而不在3 T3或Hela细胞中。总之，我们的数据证明AFP启动子可以成为一个有用的工具，赋予肝癌细胞的肿瘤特异性自杀。

项目成果

Ito, K., Ueda, Y., Kokubun, M., Urabe, M., Inaba, T., Mano, H., Hamada, H., Kitamura, T., Mizoguchi, H., Sakata, T., Hasegawa, M., and Ozawa, K.: "Development of a novel selective amplifier gene for controllable expansion of transduced hematopoietic cells

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Ohya, K.、Kajigaya, S.、Yamashita, Y.、Miyazato, A.、Hatake, K.、Miura, Y.、Ikeda, U.、Shimada, K.、Ozawa, K. 和 Mano, H.：