Abstract
Aim:
To evaluate the role of glycogen synthase kinase-3β (GSK-3β) in the induced differentiation of human glioblastoma cells.
Methods:
Cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation assay. The protein level of p-GSK-3β, GSK-3β, glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) were determined using Western blots. The overexpression of mutant GSK-3β was analyzed by immunocytochemistry.
Results:
The biotoxin cholera toxin is capable of inducing differentiation of U87-MG human glioblastoma cells, which is characterized by morphological changes to astrocytic phenotype, increase in differentiation marker protein GFAP and decrease in proliferation. GSK-3β activation is induced during this differentiation. Small interfering RNA against GSK-3β suppresses the induced-differentiation in U87-MG cells. Conversely, overexpression of a constitutively active form of human GSK-3β (pcDNA3-GSK-3β-S9A) mutant leads to differentiation of U87-MG cells.
Conclusion:
Our findings suggest that GSK-3β plays an important role in astrocytic differentiation of human glioblastoma cells and may be a novel therapeutic target in the malignant tumor.
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Acknowledgements
This study was supported by National Natural Science Foundation of China (No 30830111 and 30801408), National Natural Science Foundation of Guangdong Province (No 8451008901000297), Chinese Postdoctoral Science Foundation (No 20080430801 and 200801266), Special Foundation, Chinese Postdoctoral Science (No 200801266) and Guangzhou Scientific and Technological Programs (No 2008Z1-E561).
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Li, Y., Lu, Hm., Li, G. et al. Glycogen synthase kinase-3β regulates astrocytic differentiation of U87-MG human glioblastoma cells. Acta Pharmacol Sin 31, 355–360 (2010). https://doi.org/10.1038/aps.2010.10
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DOI: https://doi.org/10.1038/aps.2010.10
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