Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

文献类型： 外文期刊

第一作者： Wang, Jing

作者： Wang, Jing;Lv, Xiao-Wen;Shi, Jie-Ping;Hu, Xiao-Song

作者机构：

关键词： ceramide;cell cycle arrest;human hepatocarcinoma cells;p21;CyclinD1;CDK7;PPAR gamma;ERK

期刊名称：WORLD JOURNAL OF GASTROENTEROLOGY （ 影响因子：5.742； 五年影响因子：5.044 ）

ISSN： 1007-9327

年卷期： 2007 年 13 卷 7 期

页码：

收录情况： SCI

摘要： 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 PPAR gamma was upregulated. Addition of GW9662, which is a PPAR gamma 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 PPAR gamma activation. The ERK signaling pathway was involved in this process. (c) 2007 The WIG Press. All rights reserved.

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