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Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor.

Shi W, Siemann DW - Br. J. Cancer (2002)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Therapeutics, University of Florida, Box 100267, 1600 SW Archer Road, Gainesville, FL 32610, USA.

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VEGF levels in culture medium of Caki-1 tumour cells treated with different antisense PS-ODNs. The cells were either untreated (Untreated) or treated with delivery vehicle only (DOTAP), a 1 μM dose of control PS-ODNs sequences (Scramble, Sense and Inverted) or a 1 μM dose of antisense PS-ODNs targeted to a specific sequence of VEGF mRNA (V515). Each bar represents the mean±s.e. of three independent experiments. The star indicates a significant difference from the untreated or control treated groups (P<0.05, student's t-test). The 100% VEGF expression level of the untreated group corresponds to ∼850 pg ml−1 106 cells−1.
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fig1: VEGF levels in culture medium of Caki-1 tumour cells treated with different antisense PS-ODNs. The cells were either untreated (Untreated) or treated with delivery vehicle only (DOTAP), a 1 μM dose of control PS-ODNs sequences (Scramble, Sense and Inverted) or a 1 μM dose of antisense PS-ODNs targeted to a specific sequence of VEGF mRNA (V515). Each bar represents the mean±s.e. of three independent experiments. The star indicates a significant difference from the untreated or control treated groups (P<0.05, student's t-test). The 100% VEGF expression level of the untreated group corresponds to ∼850 pg ml−1 106 cells−1.

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


Inhibition of renal cell carcinoma angiogenesis and growth by antisense oligonucleotides targeting vascular endothelial growth factor.

Shi W, Siemann DW - Br. J. Cancer (2002)

VEGF levels in culture medium of Caki-1 tumour cells treated with different antisense PS-ODNs. The cells were either untreated (Untreated) or treated with delivery vehicle only (DOTAP), a 1 μM dose of control PS-ODNs sequences (Scramble, Sense and Inverted) or a 1 μM dose of antisense PS-ODNs targeted to a specific sequence of VEGF mRNA (V515). Each bar represents the mean±s.e. of three independent experiments. The star indicates a significant difference from the untreated or control treated groups (P<0.05, student's t-test). The 100% VEGF expression level of the untreated group corresponds to ∼850 pg ml−1 106 cells−1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2364273&req=5

fig1: VEGF levels in culture medium of Caki-1 tumour cells treated with different antisense PS-ODNs. The cells were either untreated (Untreated) or treated with delivery vehicle only (DOTAP), a 1 μM dose of control PS-ODNs sequences (Scramble, Sense and Inverted) or a 1 μM dose of antisense PS-ODNs targeted to a specific sequence of VEGF mRNA (V515). Each bar represents the mean±s.e. of three independent experiments. The star indicates a significant difference from the untreated or control treated groups (P<0.05, student's t-test). The 100% VEGF expression level of the untreated group corresponds to ∼850 pg ml−1 106 cells−1.
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

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Therapeutics, University of Florida, Box 100267, 1600 SW Archer Road, Gainesville, FL 32610, USA.

Show MeSH
Related in: MedlinePlus