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Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation

Cancer Gene Therapy volume 11, pages 625–632 (2004)Cite this article

Abstract

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.

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Acknowledgements

We thank Ms A Shioya and Ms H Kizu for excellent technical assistance and advice. This work was supported by Grants-in-Aid for 14571176 and the 21st century COE (Center of excellence) program from the Japanese Ministry of Education, Culture, sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Department of Academic Surgery (M9), Graduate School of Medicine, Chiba University 1-8-1, Inohana, Chuou-ku, Chiba-city, 260-8670, Chiba, Japan

    Masaya Uesato, Yoshio Gunji, Shinichi Miyazaki, Tooru Shiratori, Hisahiro Matsubara, Hideaki Shimada & Takenori Ochiai

  2. Department of Molecular Diagnosis (F8), Graduate School of Medicine, Chiba University 1-8-1, Inohana, Chuou-ku, Chiba-city, 260-8670, Chiba, Japan

    Takeshi Tomonaga & Fumio Nomura

  3. Department of Endoscopic Diagnostics and Therapeutics, Graduate School of Medicine, Chiba University 1-8-1, Inohana, Chuou-ku, Chiba-city, 260-8670, Chiba, Japan

    Teruo Kouzu

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  1. Masaya Uesato
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Correspondence to Yoshio Gunji.

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Uesato, M., Gunji, Y., Tomonaga, T. et al. Synergistic antitumor effect of antiangiogenic factor genes on colon 26 produced by low-voltage electroporation. Cancer Gene Ther 11, 625–632 (2004). https://doi.org/10.1038/sj.cgt.7700740

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