Acta Pharmacologica Sinica (2010) 31: 355–360; doi: 10.1038/aps.2010.10; published online 15 February 2010

Yan LI^{1, 2, #}, Hui-min LU^{2, #}, Gang LI^{1, *}, Guang-mei YAN^{2, *}

¹Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China; ²Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China

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.