Yan Li1, Hui-min Lu, Gang Li, Guang-mei Yan. 1. Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Abstract
AIM: To evaluate the role of glycogen synthase kinase-3beta (GSK-3beta) in the induced differentiation of human glioblastoma cells. METHODS: Cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation assay. The protein level of p-GSK-3beta, GSK-3beta, glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) were determined using Western blots. The overexpression of mutant GSK-3beta 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-3beta activation is induced during this differentiation. Small interfering RNA against GSK-3beta suppresses the induced-differentiation in U87-MG cells. Conversely, overexpression of a constitutively active form of human GSK-3beta (pcDNA3-GSK-3beta-S9A) mutant leads to differentiation of U87-MG cells. CONCLUSION: Our findings suggest that GSK-3beta plays an important role in astrocytic differentiation of human glioblastoma cells and may be a novel therapeutic target in the malignant tumor.
AIM: To evaluate the role of glycogen synthase kinase-3beta (GSK-3beta) in the induced differentiation of humanglioblastoma cells. METHODS: Cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation assay. The protein level of p-GSK-3beta, GSK-3beta, glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) were determined using Western blots. The overexpression of mutant GSK-3beta was analyzed by immunocytochemistry. RESULTS: The biotoxin cholera toxin is capable of inducing differentiation of U87-MG humanglioblastoma cells, which is characterized by morphological changes to astrocytic phenotype, increase in differentiation marker protein GFAP and decrease in proliferation. GSK-3beta activation is induced during this differentiation. Small interfering RNA against GSK-3beta suppresses the induced-differentiation in U87-MG cells. Conversely, overexpression of a constitutively active form of humanGSK-3beta (pcDNA3-GSK-3beta-S9A) mutant leads to differentiation of U87-MG cells. CONCLUSION: Our findings suggest that GSK-3beta plays an important role in astrocytic differentiation of humanglioblastoma cells and may be a novel therapeutic target in the malignant tumor.
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