期刊
EXCLI JOURNAL
卷 11, 期 -, 页码 68-77出版社
EXCLI JOURNAL MANAGING OFFICE
关键词
LY294002; glioblastoma; differentiation; invasion; GSK-3 beta; MMP
类别
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 protein and inhibition of proliferation. Small interfering RNA against glycogen synthase kinase-3 beta (GSK-3 beta) 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-3 beta and MMP respectively.
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