GENE THERAPY TARGETTING FOR GLUCOSE METABLOLISM IN PACREAS CANCER

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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.