Inhibition of TC-1 tumor progression by cotransfection of Saxatilin and IL-12 genes mediated by lipofection or electroporation.
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.
Department of Biomedical Laboratory Science, Yonsei University, Wonju 220-710, Republic of Korea. parkys@yonsei.ac.kr
Y S
YS
Park
K S
KS
Kim
Y K
YK
Lee
J S
JS
Kim
J Y
JY
Baek
L
L
Huang
D000818:Animals; D015153:Blotting, Western; D018450:Disease Progression; D019483:Disintegrins / Q000235:genetics*; D004359:Drug Therapy, Combination; D018274:Electroporation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D018664:Interleukin-12 / Q000235:genetics*; D008081:Liposomes; D008175:Lung Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D013601:T-Lymphocytes / Q000473:pathology; D014162:Transfection
D019483:Disintegrins; D008081:Liposomes; C459080:saxatilin; D018664:Interleukin-12