Sorafenib inhibits signal transducer and activator of transcription 3 signaling associated with growth arrest and apoptosis of medulloblastomas.

摘要: Medulloblastomas are the most frequent malignant brain tumors in children. Sorafenib (Nexavar, BAY43-9006), a multi-kinase inhibitor, blocks cell proliferation and induces apoptosis variety of tumor cells. inhibited induced two established lines (Daoy D283) primary culture (VC312) human medulloblastomas. In addition, sorafenib phosphorylation Signal Transducer Activator Transcription 3 (STAT3) both The inhibition phosphorylated STAT3 (Tyr705) occurs dose- time-dependent manner. contrast, AKT (protein kinase B) was only decreased D283 VC312 medulloblastoma cells MAPKs (ERK1/2) were not by these Both D-type cyclins (D1, D2, D3) E-type cyclin down-regulated sorafenib. Also, expression anti-apoptotic protein Mcl-1, member Bcl-2 family, correlated with Finally, suppressed growth mouse xenograft model. Together, our data demonstrate that signaling as well cycle regulatory proteins, associated induction These findings provide rationale for treatment pediatric medulloblastomas