Evaluation of Novel Anti-VEGF Molecules in the Animal Model of Human Lung Cancer
Evaluation of Novel Anti-VEGF Molecules in the Animal Model of Human Lung Cancer
Sanjukta Chakrabarti1, Colin J. Barrow2, Rupinder K. Kanwar3, Venkata Ramana1*, Rakesh N. Veedu4,5 and Jagat R. Kanwar3*
ABSTRACT
Abnormal angiogenesis or the formation of aberrant vasculature in humans, may lead to various pathological conditions including tumor development. The most important factor implicated in the angiogenic processes is vascular endothelial growth factor (VEGF) protein and its family of ligands and receptors (VEGFRs). Survival, proliferation, migration and invasion of endothelial cells which give rise to the vascular network, is mediated through VEGF/VEGFR activation of the signal transduction pathways. Thus blocking VEGF is an efficient strategy for blocking tumor angiogenesis. Several anti-VEGF drugs have been developed over the last two decades and some are still at different development stages of pre-clinical and clinical trials. In this study, we explored the anti-angiogenic properties of three anti-VEGF molecules such as two fusion proteins, VEGF TrapR1R2 and VEGFR1(D1-D3)-Fc, and one DNA aptamer, RNV66, in an in vivo model of human A549 lung cancer. VEGF TrapR1R2 is a commercial anti-angiogenic fusion protein. Our earlier studies demonstrated the anti-angiogenic and anti-proliferative activities of VEGFR1(D1-D3)-Fc and RNV66 in in vitro functional assays. We compared the anti-tumorigenic properties of these three molecules for tumor volume reduction in xenotransplanted SCID mice and by histopathological and immunohistochemical analyses. Our results demonstrated that fusion protein VEGFR1(D1-D3)-Fc efficiently inhibited
the lung cancer growth in vivo. Although the aptamer RNV66 was not found to be as efficient in this study, the results were also not surprising as the aptamer was administered naked and at low dose. As these are only our preliminary studies, a detailed investigation is planned using multiple doses, chitosan nanoparticle conjugated aptamer inline with the previous report on RNV66, and an approved VEGF inhibitor Avastin. Overall, the findings highlight that VEGFR1(D1-D3)-Fc can also serve as a potential anti-angiogenic molecule.
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