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LY294002 induces differentiation and inhibits invasion of glioblastoma cells by targeting GSK-3beta and MMP.

Tian Q, Cui H, Li Y, Lu H - EXCLI J (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Tianjin Children's Hospital, Tianjin 300074, China.

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 protein 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.

No MeSH data available.


Related in: MedlinePlus

Akt inhibition and GSK-3β activation induced by LY294002 in C6 glioblastoma cells. Immunoblot of p-AktSer473, Akt, p-GSK-3βser9 and GSK-3β levels in C6 cells treated with 20 μM LY294002 for the indicated time.
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Figure 3: Akt inhibition and GSK-3β activation induced by LY294002 in C6 glioblastoma cells. Immunoblot of p-AktSer473, Akt, p-GSK-3βser9 and GSK-3β levels in C6 cells treated with 20 μM LY294002 for the indicated time.

Mentions: We first confirmed the PI3K-Akt inhibitory activity of LY294002 at concentrations used in the current study. Glioblastoma cells were treated with 20 μM LY294002 and the effect on Akt activation was assessed by Western blot analysis. As shown in Figure 3(Fig. 3), LY294002 treatment effectively inhibited Akt phosphorylation following 6 h drug treatment.


LY294002 induces differentiation and inhibits invasion of glioblastoma cells by targeting GSK-3beta and MMP.

Tian Q, Cui H, Li Y, Lu H - EXCLI J (2012)

Akt inhibition and GSK-3β activation induced by LY294002 in C6 glioblastoma cells. Immunoblot of p-AktSer473, Akt, p-GSK-3βser9 and GSK-3β levels in C6 cells treated with 20 μM LY294002 for the indicated time.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920038&req=5

Figure 3: Akt inhibition and GSK-3β activation induced by LY294002 in C6 glioblastoma cells. Immunoblot of p-AktSer473, Akt, p-GSK-3βser9 and GSK-3β levels in C6 cells treated with 20 μM LY294002 for the indicated time.
Mentions: We first confirmed the PI3K-Akt inhibitory activity of LY294002 at concentrations used in the current study. Glioblastoma cells were treated with 20 μM LY294002 and the effect on Akt activation was assessed by Western blot analysis. As shown in Figure 3(Fig. 3), LY294002 treatment effectively inhibited Akt phosphorylation following 6 h drug treatment.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Tianjin Children's Hospital, Tianjin 300074, China.

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 protein 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.

No MeSH data available.


Related in: MedlinePlus