Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma.

摘要: The tumor microenvironment plays a critical role in modulating malignant behavior and can dramatically influence cancer treatment strategies. We investigated whether statins inhibit the expression of vascular endothelial growth factor (VEGF), basic fibroblast (bFGF), hepatocyte (HGF), transforming factor-β (TGF-β) mRNA mouse osteosarcoma cell line LM8. found that significantly inhibited expressions bFGF, HGF, TGF-β, TGF-β secretions at concentrations did not have antiproliferative effects on LM8 cells, but had no effect secretion VEGF. inhibition expression, was reversed when geranylgeranyl pyrophosphate (GGPP), an intermediate mevalonate pathway, used combination with statins. Furthermore, reduced membrane localization K-Ras, phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), Akt. Our research indicates GGPP biosynthesis then signal transduction Ras/ERK Ras/Akt pathways, thereby inhibiting cells. These results suggest are potentially useful as anti-angiogenic agents for osteosarcoma.