Abstract
Background: Statins are thought to have tumorolytic properties, reducing angiogenesis by inhibiting pro-angiogenic factors and inducing apoptosis of mural pericytes within the tumor vascular tree. Materials and Methods: An orthotopic mouse glioblastoma (GL-26) model was used to investigate the effect of simvastatin on glioblastoma vasculature in vivo. GL-26 cells were implanted into the striatum of C5LKa mice treated with either control, low- or high-dose simvastatin. Brains were analyzed for necrotic volume, apoptosis, morphology and pericytic cells within the vascular tree. Results: Low-dose simvastatin increased necrosis and apoptosis compared to both control and high-dose simvastatin groups. High-dose simvastatin increased vessel caliber by reducing pericytic cells along the tumor vessel wall compared to both control and low-dose simvastatin groups. Conclusion: Simvastatin has a dual effect on tumorigenesis. At high doses, it may worsen instead of ‘normalizing’ tumor angio-architecture, albeit low doses affect tumor cell survival by promoting necrosis and apoptosis.
- Received May 20, 2009.
- Revision received October 26, 2009.
- Accepted November 2, 2009.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved