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.

Wannenes, F., Ciafré, S.A., Niola, F., Frajese, G., & Farace, M.G. (2005). Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo. CANCER GENE THERAPY, 12(12), 926-934 [10.1038/sj.cgt.7700862].

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

CIAFRE', SILVIA ANNA;FRAJESE, GIOVANNI;FARACE, MARIA GIULIA
2005-12

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/13
English
Con Impact Factor ISI
Male; Cell Proliferation; Vascular Endothelial Growth Factor A; RNA Interference; Base Sequence; Rats; Plasmids; Animals; Humans; Cell Line, Tumor; Xenograft Model Antitumor Assays; Prostatic Neoplasms; Mice; Genetic Vectors; Mice, SCID; Molecular Sequence Data; Sequence Alignment
Wannenes, F., Ciafré, S.A., Niola, F., Frajese, G., & Farace, M.G. (2005). Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo. CANCER GENE THERAPY, 12(12), 926-934 [10.1038/sj.cgt.7700862].
Wannenes, F; Ciafre', Sa; Niola, F; Frajese, G; Farace, Mg
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/9179
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