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Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery

Gene Therapy volume 10, pages 123–130 (2003)Cite this article

Abstract

Tumors require ongoing angiogenesis to support their growth. Inhibition of angiogenesis by production of antiangiogenic factors should be a viable approach for cancer gene therapy. In this study, we investigated whether intravenous administration of endostatin gene complexed with a cationic vector (GL67/DOPE or PEI22K) could inhibit the development of lung tumors in mice injected i.v. with NFSa Y83 fibrosarcoma cells (5×105) which frequently form lung metastasis. mRNA and protein of the transfected gene were produced in the lung and other organs of the transfected mice as assessed by immunohistochemistry, Western blotting and reverse transcription-polymerase chain reaction. Single intravenous injection of the endostatin gene (60 μg) complexed with either GL67/DOPE or PEI22K on day 3 or day 7 after fibrosarcoma cell inoculation significantly inhibited tumor formation in the lung as evidenced by the reduced number of lung tumors and lung weight, and prolonged survival of the endostatin gene-transfected mice compared with control mice. These findings suggested that the endostatin gene therapy, using cationic vector-mediated intravenous gene transfer, might be a feasible strategy for organ-targeted prevention and regulation of possible disseminated cancers.

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Acknowledgements

We are grateful to Dr RK Scheule, Ms L Leontie and Ms K Girard (Genzyme Corporation) for providing GL67/DOPE. We thank Ms A Miyazaki, Ms M Nishio and Ms S Makino for technical assistance, and Dr Koichi Ando for providing murine fibrosarcoma cell line NFSa Y83.

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Authors and Affiliations

  1. Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya, Japan

    Y Nakashima, M Yano, Y Kobayashi, S Moriyama, H Sasaki, T Toyama, H Yamashita, I Fukai, H Iwase, Y Yamakawa & Y Fujii

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  1. Y Nakashima
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  2. M Yano
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This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture of Japan

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Nakashima, Y., Yano, M., Kobayashi, Y. et al. Endostatin gene therapy on murine lung metastases model utilizing cationic vector-mediated intravenous gene delivery. Gene Ther 10, 123–130 (2003). https://doi.org/10.1038/sj.gt.3301856

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