GENE THERAPY TARGETTING FOR GLUCOSE METABLOLISM IN PACREAS CANCER

针对胰腺癌葡萄糖代谢的基因治疗

• 批准号: 13670540
• 负责人: SATOH Shinobu
• 金额: $ 2.3万
• 依托单位: Yokohama City University Hospital
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670540/
• 关键词: glucose transporter; pancreatic cancer; gene therapy; proliferation; invasion; p21; MAPkinase; cell cycle; 糖輸送活性; 細胞増殖

We attempted to suppress glucose transporter 1 (GLUT1) expression by transfecting various human pancreas cancer cell line (Capan-2, PANC-1, AsPC-1, BxPC3) with cDNA for antisense GLUT1. Glucose transport was significantly decreased in cells with antisense GLUT1 compared with wild-type cells or cells with vector aione. The cell proliferation of the Capan-2 (aGLUT1) which controlled a GLUT1 expression was measured with MTT method. Compared in the wild strain (Wt), it shows about 35% of control. Glucose transport activity showed a decrease up to 24%. MAP Kinase activity with a aGLUT1 cell line revealed remarkably decrease. Suppression of GLUT1 mRNA resulted in a decreased number of cells in the S phase in the analysis of the cell cycle. This was accompanied by overexpression of p21 protein. The effect which even other human pancreas cancer cell lines, PANC-1, AsPC-1, and BxPC-3, were similar results and tend to depend on the amount of GLUT1 expression.These results suggest that antisense GLUT1 mRNA inhibits tumor growth through a G(1) arrest and the expression of antisense GLUT1 mRNA via gene therapy can be used as a fool in the treatment of pancreas cancer.

我们尝试通过用反义 GLUT1 的 cDNA 转染各种人胰腺癌细胞系（Capan-2、PANC-1、AsPC-1、BxPC3）来抑制葡萄糖转运蛋白 1 (GLUT1) 的表达。与野生型细胞或带有载体 aione 的细胞相比，带有反义 GLUT1 的细胞中的葡萄糖转运显着减少。通过MTT法测定控制GLUT1表达的Capan-2(aGLUT1)的细胞增殖。与野生株（Wt）相比，其显示出对照的约35%。葡萄糖转运活性下降高达 24%。 aGLUT1 细胞系的 MAP 激酶活性显着降低。在细胞周期分析中，抑制 GLUT1 mRNA 会导致处于 S 期的细胞数量减少。这伴随着 p21 蛋白的过度表达。甚至其他人类胰腺癌细胞系 PANC-1、AsPC-1 和 BxPC-3 的效果也相似，并且往往取决于 GLUT1 表达量。这些结果表明，反义 GLUT1 mRNA 通过 G(1) 阻滞抑制肿瘤生长，并且通过基因治疗表达反义 GLUT1 mRNA 可用于治疗胰腺癌。

项目成果

Yasuhi Kaburagi, Shinobu Satoh et al.: "Protection of insulin receptor substrate-3 from staurosporine-induced apoptosis."Biochem Biophys Res Commun 300. 2. 371-377 (2003)

Yasuhi Kaburagi、Shinobu Satoh 等人：“保护胰岛素受体底物 3 免受星形孢菌素诱导的细胞凋亡。”Biochem Biophys Res Commun 300. 2. 371-377 (2003)

Youki Tsuji, et al.: "Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-i null mice"Diabetes. 50. 1455-1463 (2001

Youki Tsuji等人：“与磷脂酰肌醇3激酶活性相关的胰岛素受体底物家族蛋白的亚细胞定位以及来自IRS-i无效小鼠的原代小鼠脂肪细胞中脂解作用的改变”糖尿病。

Kazuhiro Eto et al.: "Phosphatidylinositol 3-kinase Suppresses glucose-stimulated insulin secretion by affecting post-cytosolic [Ca(2+)] elevation signals"Diabetes. 51. 87-97 (2002)

Kazuhiro Eto 等人：“磷脂酰肌醇 3-激酶通过影响胞质后 [Ca(2)] 升高信号来抑制葡萄糖刺激的胰岛素分泌”糖尿病。

Jun Togawa, et al.: "Lacioferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance"Am J Physiol Gastrointest Liver Physiol. 283・1. G187-G195 (2002)

Jun Tokawa 等人：“乳铁蛋白通过调节免疫系统和纠正细胞因子失衡减少大鼠结肠炎”Am J Physiol Gastrointest Liver Physiol 283·1。

Youki Tsuji et al: "Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adiposities from IRS-1 null mice."Diabetes 50 .6. 1455-1463 (20

Youki Tsuji 等人：“与磷脂酰肌醇 3 激酶活性相关的胰岛素受体底物家族蛋白的亚细胞定位以及 IRS-1 无效小鼠原发性小鼠脂肪分解的改变。”糖尿病 50 .6。