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Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo

Cancer Gene Therapy volume 12, pages 926–934 (2005)Cite this article

Abstract

RNA interference technology is emerging as a very potent tool to obtain a cellular knockdown of a desired gene. In this work we used vector-based RNA interference to inhibit vascular endothelial growth factor (VEGF) expression in prostate cancer in vitro and in vivo. We demonstrated that transduction with a plasmid carrying a small interfering RNA targeting all isoforms of VEGF, dramatically impairs the expression of this growth factor in the human prostate cancer cell line PC3. As a consequence, PC3 cells loose their ability to induce one of the fundamental steps of angiogenesis, namely the formation of a tube-like network in vitro. Most importantly, our “therapeutic” vector is able to impair tumor growth rate and vascularization in vivo. We show that a single injection of naked plasmid in developing neoplastic mass significantly decreases microvessel density in an androgen-refractory prostate xenograft and is able to sustain a long-term slowing down of tumor growth. In conclusion, our results confirm the basic role of VEGF in the angiogenic development of prostate carcinoma, and suggest that the use of our vector-based RNA interference approach to inhibit angiogenesis could be an effective tool in view of future gene therapy applications for prostate cancer.

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Acknowledgements

We are particularly grateful to Bina Santoro for her critical review and helpful comments. We thank Paul D Good, Engelke lab., University of Michigan Medical School, Ann Arbor, Michigan, USA, for providing us with pAVU6+27 vector. We thank T Delli Castelli and G Bonelli for excellent technical assistance. This study was funded in part by grants from the Italian Ministry of Instruction, University and Scientific Research (MIUR), FIRB and COFIN, and from the Italian Ministry of Health, to MGF and to SAC.

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Author notes

  1. Francesca Wannenes and Silvia Anna Ciafré: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata”, Via Montpellier, 1 00133, Rome, Italy

    Francesca Wannenes, Silvia Anna Ciafré, Francesco Niola & Maria Giulia Farace

  2. Department of Internal Medicine and Endocrinology, University of Rome “Tor Vergata”, Via Montpellier, 1 00133, Rome, Italy

    Francesca Wannenes & Gaetano Frajese

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  1. Francesca Wannenes
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Correspondence to Maria Giulia Farace.

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Wannenes, F., Ciafré, S., Niola, F. et al. Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo. Cancer Gene Ther 12, 926–934 (2005). https://doi.org/10.1038/sj.cgt.7700862

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