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

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

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.

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. https://doi.org/10.3892/or-00000954

• Journal Article Type: Article
• Acceptance Date: Oct 31, 2010
• Publication Date: Oct 8, 2010
• Journal: ONCOLOGY REPORTS
• Print ISSN: 1021-335X
• Publisher: Spandidos Publications
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 4
• Pages: 1049-1058
• 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
• Public URL: https://hull-repository.worktribe.com/output/400103
• Publisher URL: https://www.spandidos-publications.com/or/24/4/1049