Effect Of GSK-3β On The Proliferation And Metastasis Of Human Gastric Carcinoma Cell And Theirs Mechanism

Objective:To observe the effect of GSK-3βon the proliferation and metastasis of human gastric carcinoma cell and investigate theirs mechanism initially.Methods:SCG-7901 cells were cultured in medium containing LY294002 with or without lithium chloride in different concentrations in vitro.Cell proliferation was tested by MTT assay;the expression of total GSK-3βand p-GSK-3β^ser9 were detected in protein level by western blotting;cell cycle and apoptosis were analyzed by flow cytomery;the mRNA level of CyclinD1 were detected by RT-PCR;the expression of CyclinD 1,c-Myc,caspase3,E-cadherin andβ-catenin were measured with S-P immunohistochemistry and the cell-ground substance adhesion was tested by cell adherence assay.Results:LY294002 inhibits the cell proliferation in a concentration and time dependent manner.The expression of total GSK-3βwas a constant and the protein level of p-GSK-3β^sr9 was down regulated in a dose manner of LY294002 after be exposured to LY294002 for 72h.The result of Flow cytomery showed that the cell was arrested at G0/G1 phase and had an apoptotic peak.The expression of CyclinD1,c-Myc,β-catenin and the cellground substance adhesion rate were negatively regulated,the E-cadherin level and caspase3 level were positively regulated.The effects by the LY294002 which mentioned above were partially abrogated by lithium chloride.Conclusion:GSK-3βcould negatively regulate the proliferation of human gastric carcinoma cell.The associated mechanism may be that GSK-3βcould negatively regulated CyclinD1 and c-Myc leading to cycle arrest and positively regulated caspase3 inducing apoptosis.GSK-3βcould take part in inhibiting the metastasis of human gastric carcinoma cell by positively regulating the expression of E-cadherin and advancing the degradation ofβ-catenin.