Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation.
Antiangiogenic factors are potent endothelial cell growth inhibitors that have been shown to inhibit angiogenesis in vitro and tumor growth in mice. We have demonstrated the synergistic antitumor effect of antiangiogenic genes (mouse angiostatin: pBLAST-mAngio; and mouse endostatin: p-BLAST42-mEndo XV) delivered to tumors by low-voltage electroporation in mouse colon 26 models. A synergistic antitumor effect was strongly suggested by in vivo tumor growth kinetics, as well as in survival studies with the mice. RT-PCR confirmed that the fragments of each gene were transferred by low-voltage electroporation in the tumor. Decreased microvessel density measurements in tumors also confirmed the efficacy of the synergistic antitumor effect of both genes. Significant growth inhibition was observed in mice treated with a 1:1 proportion of angiostatin and endostatin genes, and the order of the both genes transferred (first the endostatin gene, followed 1 week later by the angiostatin gene) had a profound inhibitory effect on tumor growth. These data suggest that in vivo delivery of antiangiogenic genes with low-voltage electroporation could be a possible therapeutic strategy for established solid tumors when both genes were applied in combination.
Uesato
Masaya
M
Department of Academic Surgery (M9), Graduate School of Medicine, Chiba University 1-8-1, Inohana, Chuou-ku, Chiba-city, Chiba 260-8670, Japan.
Gunji
Yoshio
Y
Tomonaga
Takeshi
T
Miyazaki
Shinichi
S
Shiratori
Tooru
T
Matsubara
Hisahiro
H
Kouzu
Teruo
T
Shimada
Hideaki
H
Nomura
Fumio
F
Ochiai
Takenori
T
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D043168:Angiostatins / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004357:Drug Synergism; D018274:Electroporation; D043169:Endostatins / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D043168:Angiostatins; D008156:Luciferases