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AIM: To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS: 3- (4, 5)-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT) assay, plasmid transfection, reporter assay, FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS: C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest. During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1/2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARγ was upregulated. Addition of GW9662, which is a PPARγ specific antagonist, could reserve the modulation action on CDK7. CONCLUSION: Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARγ activation. The ERK signaling pathway was involved in this process.
AIM: To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells. Possible molecular mechanisms were explored. METHODS: 3- (4,5) -dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide (MTT) assay , plasmid transfection, reporter assay, FACS and Western blotting analyzes were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells. RESULTS: C2-ceramide was found to inhibit the growth of Bel7402 cells by During the process, the expression of p21 protein increased, while that of cyclinD1, phospho-ERK1 / 2 and c-myc decreased. Furthermore, the level of CDK7 was downregulated, while the transcriptional activity of PPARγ was upregulated. Addition of GW9662, which is a PPARγ specific antagonist, could reserve the modulation action on CDK7. CONCLUSION: Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7, at least partly, through PPARγ activation. The ERK signaling pathway was involved in this process.