Department of Neurosurgery, Stanford University Medical Center, 1201 Welch Road, P310, Stanford, CA 94305-5327, USA.
Anticancer Res. 2009 Dec;29(12):4901-8.
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.
他汀类药物被认为具有肿瘤溶解特性，通过抑制促血管生成因子和诱导肿瘤血管树中层细胞周细胞凋亡来减少血管生成。
使用原位小鼠脑胶质瘤（GL-26）模型来研究辛伐他汀对体内脑胶质瘤血管的影响。将 GL-26 细胞植入 C5LKa 小鼠的纹状体中，并用对照、低剂量或高剂量辛伐他汀处理。分析大脑中的坏死体积、凋亡、形态和血管树中的周细胞。
与对照和高剂量辛伐他汀组相比，低剂量辛伐他汀增加了坏死和凋亡。与对照和低剂量辛伐他汀组相比，高剂量辛伐他汀通过减少肿瘤血管壁上的周细胞来增加血管口径。
辛伐他汀对肿瘤发生具有双重作用。高剂量时，它可能会使肿瘤血管结构恶化而不是“正常化”，尽管低剂量通过促进坏死和凋亡来影响肿瘤细胞的存活。
