Synergistic antitumoral effect of IL-12 gene cotransfected with antiangiogenic genes for angiostatin, endostatin, and saxatilin.
Previously, it was reported that the cotransfection of angiostatin K1-3, endostatin, and saxatilin genes using cationic liposomes significantly inhibited tumor progression. IL-12 is a well-known immune modulator that promotes Th1-type antitumor immune responses and also induces antiangiogenic effects. In this study, we have examined the antitumoral function of the IL-12 gene cotransfected with antiangiogenic genes for angiostatin K1-3, endostatin, and saxatilin by O,O'-dimyristyl-N-lysyl glutamate (DMKE) cationic liposomes in a mouse tumor model. According to our results, the administration of the IL-12 gene or the genes for angiostatin K1-3, endostatin, and saxatilin exhibited effective inhibition of B16BL6 melanoma growth in mice. In particular, intravenous administration of the IL-12 gene along with intratumoral administration of the three antiangiogenic genes synergistically inhibited the B16BL6 tumor growth. These results suggest that systemically expressed IL-12 enhances antitumoral efficacy of locally expressed antiangiogenic proteins.
Department of Biomedical Laboratory Science, Korea Nazarene University, Cheonan, Korea.
Hong Sung
HS
Kim
Hwa Yeon
HY
Jeong
Yeon Kyung
YK
Lee
Keun Sik
KS
Kim
Yong Serk
YS
Park
D043168:Angiostatins / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D004151:Dipeptides / Q000008:administration & dosage / Q000737:chemistry; D019483:Disintegrins / Q000096:biosynthesis / Q000235:genetics*; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008546:Melanoma, Experimental / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D014162:Transfection / Q000379:methods
D004151:Dipeptides; D019483:Disintegrins; D043169:Endostatins; D008081:Liposomes; C515778:O,O'-dimyristyl-N-lysyl glutamate; C459080:saxatilin; D018664:Interleukin-12; D043168:Angiostatins; D004247:DNA