Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor.
Bottom Line: Vascular endothelial growth factor has been implicated as the key factor in tumour angiogenesis.In vitro studies showed that treating Caki-1 cells with antisense phosphorothioate oligodeoxynucleotides directed against vascular endothelial growth factor mRNA led to a reduction in expressed vascular endothelial growth factor levels sufficient to impair the proliferation and migration of co-cultured endothelial cells.The observed effects were antisense sequence specific, dose dependent, and could be achieved at a low, non-toxic concentration of phosphorothioate oligodeoxynucleotides.
Affiliation: Department of Pharmacology and Experimental Therapeutics, University of Florida, Box 100267, 1600 SW Archer Road, Gainesville, FL 32610, USA.Show MeSH
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Mentions: The ability to down-regulate VEGF expression by antisense PS-ODNs treatment in Caki-1 tumour cells was first evaluated in vitro. The results showed that after 24 h treatment with 1 μM VEGF antisense PS-ODNs (V515) delivered by cationic liposome (DOTAP : DOPE), the medium VEGF level was significantly reduced to ∼35% that found in the control untreated group (from a normal of 850 pg ml−1 106 cells−1 to 300 pg ml−1 106 cells−1) (Figure 1Figure 1
Affiliation: Department of Pharmacology and Experimental Therapeutics, University of Florida, Box 100267, 1600 SW Archer Road, Gainesville, FL 32610, USA.