VEGF neutralizing antibody increases the therapeutic efficacy of vinorelbine for renal cell carcinoma.

Publication Type:

Journal Article

Source:

Journal of cellular and molecular medicine, Volume 14, Issue 3, p.647-58 (2010)

Keywords:

Animalsdigestive disease, digestive deseases Antibodies, Neutralizingdigestive disease, digestive deseases Antineoplastic Agents, Phytogenicdigestive disease, digestive deseases Antineoplastic Combined Chemotherapy Protocolsdigestive disease, digestive deseases Apoptosisdigestive disease, digestive deseases Blotting, Westerndigestive disease, digestive deseases Carcinoma, Renal Celldigestive disease, digestive deseases Cell Cycledigestive disease, digestive deseases Cell Line, Tumordigestive disease, digestive deseases Cell Proliferationdigestive disease, digestive deseases Cyclinsdigestive disease, digestive deseases Dose-Response Relationship, Drugdigestive disease, digestive deseases Drug Synergismdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Kidney Neoplasmsdigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Nudedigestive disease, digestive deseases Neovascularization, Pathologicdigestive disease, digestive deseases Proliferating Cell Nuclear Antigendigestive disease, digestive deseases Vascular Endothelial Growth Factorsdigestive disease, digestive deseases Vinblastinedigestive disease, digestive deseases Xenograft Model Antitumor Assays

Abstract:

Renal cell carcinoma (RCC) is currently one of the most treatment-resistant malignancies and affects approximately three in 10,000 people. The impact of this disease produces about 31,000 new cases in the United States per year; and 12,000 people in the United States alone die from RCC annually. Although several treatment strategies have been investigated for RCC, this cancer continues to be a therapeutic challenge. For this reason, the aim of our study is to develop a more effective combinational therapy to treat advanced RCC. We examined the effect of vinorelbine on the signalling pathways of two human renal cancer cell lines (A498 and 786-O) and also examined the in vivo effect of vinorelbine treatment alone and vinorelbine in combination with the anti-VEGF antibody 2C3 on A498 and 786-O tumour growth in nude mice. Tumour angiogenesis was measured by vWF staining, and apoptosis was determined by the TUNEL assay. We observed a significant tumour growth inhibition when using a combinational therapy of anti-VEGF antibody 2C3 and vinorelbine in both A498 and 786-O tumour-bearing mice. The results suggest a breakthrough treatment for advanced RCC.