Receptor tyrosine kinase inhibition by regorafenib/sorafenib inhibits growth and invasion of meningioma cells.

摘要: Systemic chemotherapeutic treatment for unresectable and/or aggressive meningiomas is still unsatisfying. PDGF receptor (PDGFR)-mediated activation of mitogenic signalling has been shown to be active in meningiomas. Therefore, we evaluate in vitro and in vivo the effects inhibiting PDGFR using clinically well-characterised tyrosine kinase inhibitors sorafenib or regorafenib meningioma models. IOMM-Lee cells were used assess cytotoxic effects, inhibition proliferation, induction apoptosis, as well migration motility by regorafenib. Using an orthotopic mouse xenograft model, growth monitored magnetic resonance imaging, overall survival sorafenib- regorafenib-treated mice compared with control animals was determined. Treatment malignant resulted significantly reduced cell apoptosis following treatment. Western blots showed that both drugs target phosphorylation p44/42 ERK via downregulation PDGFR. Both additionally significant invasion. In vivo, xenografts a volume (n.s.) signal enhancement MRI (mainly tumour) This translated increased time (p ≤ 0.05) mice. Analyses in vivo-grown tumours demonstrated again expression expression/phosphorylation p44/42. Sorafenib show antitumour activity targeting signalling.