Abstract
Sorafenib and Regorafenib (Fluoro-Sorafenib) are closely related multikinase inhibitors, which possess activity in the treatment of some human cancers. The potential role of both drugs in meningiomas have not been elucidated so far. Therefore, we have studied their anti-tumor activity in various in vitro meningioma models. A moderate antiproliferative activity of both drugs applied for 48 h (p < 0.001) to malignant IOMM-Lee meningioma cells was found in microtiter-tetrazolium (MTT) assays with an IC50 of 15 µM for Regorafenib and an IC50 between 7.5 and 15 µM for Sorafenib. MTT assays just reflect the number of viable cells and may thus indicate solely an inhibition of proliferation of the rapidly growing IOMM-Lee cells. However, some degree of cell death induction must have been occured, because a strong induction of nucleosome liberation (p < 0.05) was observed for both drugs by ELISA. Both drugs consistently had lower effects (MTT assay) in two syngenous derivatives of the benign SF4068 meningioma line exhibiting a massive NF2 loss (shRNA mediated) as compared to two syngenous SF4068 derivatives with NF2 wildtype. This suggests a modifying role of the NF2 status on the effects of Regorafenib and Sorafenib. Moreover, both drugs (15 µM) dramatically inhibited cell migration (gap assay, p < 0.05) and invasion (matrigel transwell assay, p < 0.01). Therefore, Sorafenib and Regorafenib seem to target preferentially meningioma cell motility and brain invasion.