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Enhanced antitumor effect of EGF R–targeted p21WAF-1 and GM-CSF gene transfer in the established murine hepatoma by peritumoral injection

Cancer Gene Therapy volume 9, pages 100–108 (2002)Cite this article

Abstract

One of the major obstacles in current cancer gene therapy is the lack of a gene delivery system with high efficiency and targetability. In this paper, a nonviral gene delivery system GE7, which was designed to target EGF receptor (EGF R) overexpressed on the surface of cancer cells through an EGF R–binding oligopeptide (GE7), was used for in vivo gene therapy in a murine subcutaneous hepatoma model. It was demonstrated that the GE7 system could target the reporter gene β-gal to EGF R–expressing hepatoma cells with high efficiency after in vitro transfection and in vivo peritumoral injection. To improve the therapeutic effect elicited by single gene transfer, human cyclin-dependent kinase inhibitor gene p21WAF-1 and murine cytokine gene GM-CSF were used simultaneously in peritumoral injection of the GE7/DNA polyplex. The results showed that combined gene transfer of p21WAF-1 and GM-CSF could inhibit the growth of pre-established tumor more effectively and prolong the survival time of hepatoma-bearing mice more significantly than the transfer of a single gene. Apoptosis in the tumor tissues were found when injected with the p21WAF-1 DNA polyplex. Prominent inflammatory infiltration was observed in the tumor tissue transfected with the GM-CSF DNA polyplex. Our data demonstrate that the GE7 system–mediated, EGF R–targeted cotransfer of p21WAF-1 and GM-CSF genes exhibit more potent antitumor effect by inducing tumor cell apoptosis and inflammatory responses.

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Acknowledgements

We thank Dr. Jingjun Li for pathological section preparation and immunohistochemistry analysis and Dr. Dian-Wen Ju for his helpful discussion. This work was supported by a grant of Biotechnology Project, National High Technology Program of China (Project No. Z-20-01-01).

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Authors and Affiliations

  1. National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, 200032, China

    Xiang Liu, Peikun Tian, Ming Yao & Jianren Gu

  2. Institute of Immunology, Second Military Medical University, Shanghai, 200433, China

    Yizhi Yu & Xuetao Cao

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  1. Xiang Liu
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Correspondence to Xuetao Cao or Jianren Gu.

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Liu, X., Tian, P., Yu, Y. et al. Enhanced antitumor effect of EGF R–targeted p21WAF-1 and GM-CSF gene transfer in the established murine hepatoma by peritumoral injection. Cancer Gene Ther 9, 100–108 (2002). https://doi.org/10.1038/sj.cgt.7700400

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