Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition.

Abstract

In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides were crucial for higher efficacy. Furthermore, the binding interaction of RNV66 with VEGF was investigated using molecular dynamic simulations leading to the first computational model of the LNA aptamer-VEGF complex blocking its interaction with VEGF-receptor.

• Authors: Stacey L Edwards, Vasanthanathan Poongavanam, Jagat R Kanwar, Kislay Roy, Kristine M Hillman, Neerati Prasad, Rikke Leth-Larsen, Michael Petersen, Maja Marušič, Janez Plavec, Jesper Wengel, Rakesh N Veedu
• Journal: Chemical communications (Cambridge, England) (Chem Commun (Camb)) Vol. 51 Issue 46 Pg. 9499-502 (Jun 11 2015) ISSN: 1364-548X [Electronic] England
• PMID: 25968110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Aptamers, Nucleotide
• Oligonucleotides
• RNV66 DNA aptamer
• Vascular Endothelial Growth Factor A
• locked nucleic acid
• Guanine

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Aptamers, Nucleotide (chemistry, pharmacology, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Female
• Guanine
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Mice, Nude
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Oligonucleotides (chemistry)
• Tumor Burden (drug effects)
• Vascular Endothelial Growth Factor A (metabolism)