Experimental Studies On The Treatment Of Pancreatic Carcinoma With Gene Co-transfection Of Human Endostatin And Antisense K-Ras Mediated By Recombinant Adenovirus

Objective: To observe the inhibitory effects of human endostatin in combination with antisense K-Ras on pancreatic carcinoma mediated by recombinant adenovirus. Methods: Two replication deficient adenovirus containing human endostatin cDNA and anti-sense cDNA against K-Ras exon 1 of SW1990 cells line respectively were constructed and named as Ad-hEnd and Ad-aK-Ras. SW1990 cells were infected by Ad-hEnd, Ad-aK-Ras and Ad-hEnd in combination with Ad-aK-Ras, then the endostatin bioactivities, proliferation and apoptosis of tumor cells, expression of vascular endothelial growth factor and the therapeutic effects in vivo were detected by a series of assays. Results: Two replication deficient adenovirus were constructed successfully. Ad-aK-Ras significantly inhibited SW1990 cell proliferation, promoted cell apoptosis and down-regulated the expression of VEGF. After infected SW1990 cells, the expression product of Ad-hEnd demonstrated bioactivities and down-regulated VEGF expression, but did not impact cell proliferation and apoptosis in vitro. Ad-hEnd, Ad-aK-Ras and Ad-hEnd in combination with Ad-aK-Ras all inhibited pancreatic tumor growth in vivo, but the greatly stronger inhibitory effect was achieved by Ad-hEnd in combination with Ad-aK-Ras. Conclusion: Purpose gene could be efficiently transformed into SW1990 cells and effectively expressed mediated by recombinant adenovirus. Both Ad-hEnd and Ad-aK-Ras inhibited the growth of SW1990 cells in vivo. When treated by Ad-hEnd in combination with Ad-aK-Ras, greater inhibitory effect would be achieved than that of treated by Ad-hEnd or Ad-aK-Ras alone.