HMG-CoA Reductase Inhibition Causes Increased Necrosis and Apoptosis in an In Vivo Mouse Glioblastoma Multiforme Model ANTICANCER RESEARCH Bababeygy, S. R., Polevaya, N. V., Youssef, S., Sun, A., Xiong, A., Prugpichailers, T., Veeravagu, A., Hou, L. C., Steinman, L., Tse, V. 2009; 29 (12): 4901-4908


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.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.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.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.

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View details for PubMedID 20044596