Abstract# 5627: Sorafenib inhibits STAT3 signaling, cell proliferation and survival of human glioblastomas

摘要: Glioblastoma multiforme (GBM) is the most common type of primary brain tumor, and is rapidly progressive with few curative treatment options. Sorafenib (Nexavar, BAY43-9006), a multi-kinase inhibitor, blocks proliferation and induces apoptosis in a variety of tumor cells. Here, we report that sorafenib (\#8804; 10 µM) strongly inhibited cell proliferation and induced apoptosis in two established cell lines (U87 and U251) and two low-passage primary cultures (PBT015 and PBT022) from human glioblastomas. Sorafenib inhibited phosphorylation of STAT3 (Signal Transducers and Activators of Transcription 3) at Tyr 705 and STAT3 DNA-binding activity in both cell lines and primary cultures. By contrast, AKT (protein kinase B) and MAPK (ERK1/2) were differentially inhibited by sorafenib in these cells. Two key cyclins (D and E) were down-regulated by sorafenib in both cell lines and primary cultures, and their …