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DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

Cancer Gene Therapy volume 16, pages 713–722 (2009)Cite this article

Abstract

Previously, we designed a DNAzyme (β1DE) targeting the human β1 integrin subunit, which efficiently digested the mRNA of the β1 integrin subunit and downregulated β1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that β1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n=20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1nu) (n=30) using prostate carcinoma cells PC-3 (n=15) and colon adenocarcinoma cells CX1.1 (n=15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting β1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.

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Acknowledgements

This work was supported by the project N401 1217 33 from the Polish Ministry of Science and Higher Education and by Projects 502-16-650 and 502-16-201.

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  1. J Niewiarowska and I Sacewicz: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Medical Biophysics, Medical University of Lodz, Lodz, Poland

    J Niewiarowska, I Sacewicz, M Wiktorska, T Wysocki & C S Cierniewski

  2. Department of Nephropathology Medical University of Lodz, Lodz, Poland

    O Stasikowska & M Wagrowska-Danilewicz

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  1. J Niewiarowska
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Correspondence to C S Cierniewski.

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Niewiarowska, J., Sacewicz, I., Wiktorska, M. et al. DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth. Cancer Gene Ther 16, 713–722 (2009). https://doi.org/10.1038/cgt.2009.13

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