The Correlation Between Wnt Signaling Pathways And Resveratrol Induced Differentiation And Apoptosis In Human Medulloblastoma Cells

Objective: 1) to study the status of Wnt signalings in human medulloblastoma cells in vivo, 2) to explore the expression and/or intracellular distribution patterns of Wnt2,β-catenin and TCF4 in human medulloblastoma cell lineUW228-2 and UW228 -3,3)to analyze the effects of resveratrol on the expressions of Wnt2,β-catenin and TCF4, 4) to elucidate the potential action mechanisms of resveratrol on medulloblastoma cell lines and 5) to provide a new experimental evidence and theoretic basis for better treatment of human medulloblastoma.Methods: The tissue microarrays (TMA) were constructed with Paraffin embedded specimens of 13 clinically collected medulloblastoma cases and their surrounding noncancerous counterparts. Test the expression levels of Wnt2,β-catenin and TCF4 in the medulloblastoma cases and their surrounding noncancerous counterparts by immunohistochemic. And, by method of immunohistochemical (IHC) stainings, RT-PCR and immunofluorescence, check the differentiations of genic expression levels of Wnt2,β-catenin and TCF4 in human medulloblastoma cell line UW228-2 and UW228-3 after being treated with resveratrol, and study the correlation between Wnt signaling pathways and resveratrol induced differentiation and apoptosis.Results: 1) Among the 13 medulloblastoma tissues so far studied, Wnt2 was expressed in 4 cases, while 5 out of 6 tumor surrounding cerebellum tissues were positive in Wnt2 expression;β-catenin and TCF4 were not found in the nucleus of medulloblastoma cells, and rarely observed in the cytoplasma and membrane; the positive rate of TCF4 in the cytoplasma of medulloblastoma tissues is 77.8% (7/9), while only 11.1%(1/9) in the nucleus. 2) Resveratrol not only suppressed the growth of medulloblastoma cell lines UW228-2 and UW228-3 cells but also induced cell differentiation and apoptosis.Wnt2,β-catenin and TCF4 were all up-regulated inUW228-2 and UW228-3 cells induced by Resveratrol, together with the nuclear co-translocation ofβ-catenin and TCF4.Conclusion: 1) Expression of Wnt2 in the medulloblastoma tissues was lower than that in noncancerous cerebellum tissues. 2)β-catenin and TCF4 were expression only in cytoplastoma and membrane, but undetectable in the nucleus of the normally cultured medulloblastoma cells. 3) Resveratrol can activate Wnt signaling pathway via up-regulating Wnt2 expression and promoting nuclear translocations ofβ-catenin and TCF4. 4) Potential links of Resveratrol-induced neuronal phenotypes and Wnt activation may remain, which awaits further elucidation.