Inhibition of TC-1 tumor progression by cotransfection of Saxatilin and IL-12 genes mediated by lipofection or electroporation

• Published in: Oncology research Vol. 18; no. 5-6; p. 203
• Main Authors: Park, Y S, Kim, K S, Lee, Y K, Kim, J S, Baek, J Y, Huang, L
• Format: Journal Article
• Language: English
• Published: United States 01-01-2009
• Subjects: Animals; Blotting, Western; Disease Progression; Disintegrins - genetics; Drug Therapy, Combination; Electroporation; Female; Gene Expression Regulation, Neoplastic - physiology; Genetic Therapy; Genetic Vectors; Interleukin-12 - genetics; Liposomes; Lung Neoplasms - genetics; Lung Neoplasms - physiopathology; Lung Neoplasms - prevention & control; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic - prevention & control; T-Lymphocytes - pathology; Transfection
• ISSN: 0965-0407
• DOI: 10.3727/096504009X12596189659088

Recently, a number of reports have demonstrated that coexpression of therapeutic genes having different anticancer mechanisms is a more effective strategy for anticancer gene therapy than single gene expression. Saxatilin, a novel disintegrin from snake venom, has recently been shown to have potent antiangiogenic functions, such as inhibition of platelet aggregation, bFGF-induced proliferation of HUVEC, and vitronectin-induced smooth muscle cell migration. IL-12 is a well-known immune modulator that promotes Thl-type antitumor immune responses and inhibits angiogenesis as well. The saxatilin and/or IL-12 genes were transfected intratumorally into C57BL/6 mice carrying TC-1 transformed mouse lung endothelial cells by either lipofection or electroporation. The plasmids encoding saxatilin and IL-12 were administered to tumor tissues via novel cationic liposomes consisting of dimyristyl-glutamyl-lysine (DMKE). On the other hand, expression of the genes was also induced by electroporation after naked pDNA injection to the tumor tissues. Lipofection of saxatilin and/or IL-12 genes appeared to be slightly more effective in inhibition of tumor growth than electroporation of the same genes. Cotransfection of saxatilin and IL-12 genes was clearly more effective than individual administration of either gene. This result implies that cotransfection of saxatilin and IL-12 genes represents an innovative modality for anticancer gene therapy.