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Sorafenib enhances the in vitro anti-endothelial effects of low dose (metronomic) chemotherapy

Murray, Alexandra; Little, Samantha J.; Stanley, Paul; Cawkwell, Lynn; Maraveyas, Anthony

Authors

Alexandra Murray

Samantha J. Little

Paul Stanley

Anthony Maraveyas A.Maraveyas@hull.ac.uk



Abstract

Angiogenesis inhibitors may enhance the effects of low dose (metronomic) chemotherapy. However, there is a wide range of novel angiogenesis inhibitors which must be tested in combinations with oral chemotherapy agents to assess the anti-endothelial and anti-cancer effects. This preliminary testing is most suited to high throughput in vitro models, rather than clinical trials. We aimed to establish an in vitro model and test the anti-endothelial and anti-cancer effects of the multi-kinase inhibitor sorafenib when used as a single agent and in combination with oral chemotherapy agents used at low concentrations. Micro-vascular endothelial cells and 3 cancer cell lines were utilised and an extended treatment strategy (96 h) was employed in order to mimic a continuous low dose anti-angiogenic chemotherapy regimen. Sorafenib significantly enhanced the anti-endothelial effect of low dose etoposide, paclitaxel and temozolomide. Sorafenib also significantly enhanced the anti-cancer effect of low dose etoposide, paclitaxel and temozolomide in SK-MEL-2 melanoma cells, producing an additive effect on inhibition of cell growth in all cases. These combinations appear to be the most promising for in vivo pre-clinical studies, with a view to testing in melanoma patients as a continuous dosing strategy, due to the in vitro additive inhibitory effect on growth seen in both endothelial and cancer cells.

Journal Article Type Article
Publication Date Oct 8, 2010
Journal ONCOLOGY REPORTS
Print ISSN 1021-335X
Electronic ISSN 1791-2431
Publisher Spandidos Publications
Peer Reviewed Peer Reviewed
Volume 24
Issue 4
Pages 1049-1058
APA6 Citation Murray, A., Little, S. J., Stanley, P., Cawkwell, L., & Maraveyas, A. (2010). Sorafenib enhances the in vitro anti-endothelial effects of low dose (metronomic) chemotherapy. Oncology Reports, 24(4), 1049-1058. doi:10.3892/or-00000954
DOI https://doi.org/10.3892/or-00000954
Keywords angiogenesis inhibitors endothelial cells low close chemotherapy metronomic chemotherapy sorafenib phase-i tumor vasculature cancer-treatment breast-cancer solid tumors cyclophosphamide angiogenesis temozolomide combination paclitaxel
Publisher URL https://www.spandidos-publications.com/or/24/4/1049