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Electrotransfer of gene encoding endostatin into normal and neoplastic mouse tissues: Inhibition of primary tumor growth and metastatic spread

Cancer Gene Therapy volume 9, pages 771–777 (2002)Cite this article

Abstract

Electroporation-mediated gene transfer relies upon direct delivery of plasmids into cells permeabilized by electric fields, a method more efficient than transfer using nonviral vectors, although neither approaches the transfer efficiency of viral vectors. Here we studied electrotransfer of a gene encoding an angiogenesis inhibitor (endostatin) into primary tumors and muscle tissues, which would serve as a site of synthesis and secretion into the bloodstream of a therapeutic antimetastatic protein with systemic effects. Optimum electroporation conditions (voltage, number and duration of impulses, separation of caliper electrodes) were first established to maximize expression of a reporter gene transferred into murine Renca kidney carcinoma, B16(F10) melanoma, or skeletal muscle tissues. In neoplastic tissues, electrotransfer of plasmid DNA was far more efficient than electroporation with lipoplexes, but no differences between naked DNA and lipoplexes were found in case of electroporated muscles. We then studied the electrotransfer of plasmid DNA carrying the endostatin gene into pre-established experimental Renca tumors. A significant inhibition of tumor growth was observed in animals electroporated with this construct. Electrotransfer of the endostatin gene into muscle tissues resulted in reduced numbers of experimental B16(F10) metastases in the lungs. This study clearly shows that electroporation may be used to efficiently transfer antiangiogenic genes into both normal and neoplastic tissues.

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Acknowledgements

The authors are grateful to H Paterak and M Krawczyk for their excellent technical assistance. They also thank R Hancock and A Sochanik for helpful discussion and critical reading of the manuscript. This study was supported by Grants: 4P05A 046 15 and Z-KBN004/PO4/98 from the Polish State Committee for Scientific Research (KBN).

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Authors and Affiliations

  1. Department of Molecular Biology, Center of Oncology, Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland

    Tomasz Cichoń, Laura Jamroży, Joanna Glogowska, Ewa Missol-Kolka & Stanisław Szala

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  1. Tomasz Cichoń
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Correspondence to Stanisław Szala.

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Cichoń, T., Jamroży, L., Glogowska, J. et al. Electrotransfer of gene encoding endostatin into normal and neoplastic mouse tissues: Inhibition of primary tumor growth and metastatic spread. Cancer Gene Ther 9, 771–777 (2002). https://doi.org/10.1038/sj.cgt.7700497

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