Sorafenib enhances the in vitro anti-endothelial effects of low dose (metronomic) chemotherapy
Murray, Alexandra; Little, Samantha J.; Stanley, Paul; Cawkwell, Lynn; Maraveyas, Anthony
Samantha J. Little
Lynn Cawkwell L.Cawkwell@hull.ac.uk
Anthony Maraveyas A.Maraveyas@hull.ac.uk
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.
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
|Journal Article Type||Article|
|Acceptance Date||Oct 31, 2010|
|Publication Date||Oct 8, 2010|
|Peer Reviewed||Peer Reviewed|
|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|
This file is under embargo due to copyright reasons.
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