The Effect Of Resveratrol On Sonic Hedgehog Signaling In Medulloblastoma And Its Neurobiological Implication

Objective: 1) observe the expression of Sonic hedgehog( Shh)signaling pathway and its target gene Nmyc in human medulloblastoma. 2) analyses the contribution of resveratrol to the expression of Sonic hedgehog(Shh)signaling pathway and its target gene Nmyc in human medulloblastoma cell line UW228-2 and UW228-3. Approach to the potential molecular mechanisms of how Res effects human MB. So we can supply theory evidence for clinical therapy to MB.Methods: 18 cases surgical specimens of human MB brain tissues and 11 cases specimens of mouse brain tissues were selected. The different tissues were indicated by the methods of paraffin tissue array-based immunohistochemical staining. Observe the expression of Shh and Gli1 in human MB and mouse brain tissues. UW228-2 and UW228-3 cell lines were cultured in DMEM with 10% fetal calf serum. Add 100μM Res for 48h. So we fixed cell slices by cool dimethylketone for ICC. And collected cells for extraction of RNA and Protein. Paralleled Western blot and RT-PCR analyses were conducted to check the expression statuses of Shh,Gli1 and Nmyc in UW228-2 and UW228-3 with or without Res.Results: 1) Among the tissue spots, 88.89%s howed positive nuclear translocation of Shh and 94.44% were positive for Gli1 staining, which were essentially observed more obviously than the control; 2) Res can obviously suppressed the growth of UW228-2 and UW228-3, induced their cell differentiation and apoptosis. Res down-regulated the expression of Shh, Gli1 and Nmyc in mRNA and protein levels. Conclusion: 1) Our current study demonstrates the expressions of Sonic hedgehog(Shh)signaling pathway and its downstream genes in human MB. 2) We first found that Res obviously suppressed the growth of UW228-2 and UW228-3, induced their cell differentiation and apoptosis, therefore, it could suppressed the expression of Shh, Gli1 and Nmyc in mRNA and protein levels. There may be some internal connection between suppression of Sonic hedgehog ( Shh ) signaling pathway and anti- medulloblastoma by Resveratrol.