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Yu Sun, Shusheng Tang, Xi Jin, Chaoming Zhang, Wenxia Zhao and Xilong Xiao Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells Journal of Applied Toxicology 33

Article first published online: 30 OCT 2012 | DOI: 10.1002/jat.2829

The aim of this study was to determine the effects of FZD on HepG2 cells by activating and inhibiting p38 MAPK signaling pathway. The cell cycle and proliferation of HepG2 cells treated with FZD were detected by flow cytometry and MTT assay in the presence or absence of p38 MAPK inhibitors (SB203580), respectively. Cyclin D1, cyclin D3, and CDK6 were detected by quantitative real-time PCR and western blot analysis. Our data showed that p38 MAPK became phosphorylated after stimulation with FZD. Activation of p38 MAPK could arise S-phase cell-cycle arrest and suppress cell proliferation. Simultaneously, inhibition of p38 MAPK significantly prevented S-phase cell-cycle arrest, increased the percentage of cell viability, and decreased the expression of cyclin D1, cyclin D3, CDK6. These results demonstrated that FZD arose S-phase cell-cycle arrest via activating p38 MAPK signaling pathway in HepG2 cells. Cyclin D1, cyclin D3, and CDK6 are target genes functioning at the downstream of p38 MAPK in HepG2 cells induced by FZD.

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