Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by inhibiting STAT3 and AKT signaling pathways.

摘要: Medulloblastomas are the most frequent malignant brain tumors in children. Sunitinib is an oral multitargeted tyrosine kinase inhibitor used clinical trials as antiangiogenic agent for cancer therapy. In this report, we show that sunitinib induced apoptosis and inhibited cell proliferation of both a short-term primary culture (VC312) established line (Daoy) human medulloblastomas. treatment resulted activation caspase-3 cleavage poly(ADP-ribose) polymerase upregulation proapoptotic genes, Bak Bim, expression survivin, antiapoptotic protein. also downregulated cyclin E, D2, D3 upregulated p21Cip1, all which involved regulating cycle. addition, it phosphorylation signal transducer activator transcription 3 (STAT3) AKT (protein B) tumor cells. Dephosphorylation STAT3 (Tyr(705)) by was helped reduction activities Janus-activated 2 Src. Additionally, sodium vanadate, protein phosphatases, partially blocked inhibition phosphorylated sunitinib. Loss after accompanied decreased downstream proteins glycogen synthase kinase-3beta mammalian target rapamycin. Expression constitutively activated mutant or myristoylated effects these migration medulloblastoma cells vitro. These findings suggest potential use pediatric