|Title:||LY294002 induces differentiation and inhibits invasion of glioblastoma cells by targeting GSK-3β and MMP|
|Abstract:||Glioblastomas are the most common and devastating primary tumors of the central nervous system, with high proliferative capacity, aggressive invasion, and resistance to conventional therapies. Differentiation therapy has emerged as a promising candidate modality. Here we show that the traditional phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 is capable of inducing differentiation of C6 glioblastoma cells characterized by morphological changes to astrocytic phenotype, increase in differentiation marker protein glial fibrillary acidic pro-tein and inhibition of proliferation. Small interfering RNA against glycogen synthase kinase-3β (GSK-3β) suppresses the induced-differentiation and invasiveness in C6 cells. LY294002 also inhibits MMP-9 expression and invasion of C6 cells, assembling the role of metalloprotease (MMP) inhibitor AG3340. Taken together, these findings suggest differentiation-inducing and invasion-inhibitory effectiveness of LY294002 in glioblastomas, most likely involving inhibition of GSK-3β and MMP respectively.|
|Appears in Collections:||Original Articles|
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