赭曲霉毒素A经p38 MAPK信号通路诱导人胃黏膜上皮细胞发生G2期阻滞

Objecitve: Ochratoxin A (OTA) is a naturally occurring mycotoxin, our previous study demonstrated that OTA evoked cell cycle arrest at G2 phase in GES-1 cells. The aim of the present study was to explore the putative role of p38 MAPK signaling pathway in OTA-induced G2 phase arrest in human gastric epithelium cells (GES-1) in vitro. Methods: After treated with different concentrations of OTA (0, 5, 10 and 20 μM) for 24 h, the expression of p38/Phospho-p38 at protein level in GES-1 cells was determined by Western blot. GES-1 cells were then preincubated with SB203580 (10 μM) for 30 min or reversely transfected with siRNA targeting p38, then the distribution of cell cycle phases was detected by Flow cytometry, and the expression of Cdc25C/p-Cdc25C, Cdc2/p-Cdc2, CyclinB1 and complex of Cdc2-CyclinB1 were detected by Western blot analysis and Immunoprecipitation. Results: OTA at different concentrations of 5, 10 and 20 μM for 24 h could activate p38 MAPK signaling pathway of GES-1 cells. p38 specific inhibitor (SB203580) and p38 siRNA transfaction blocked the down-regulation of Cdc25C/p-Cdc25C, Cdc2/p-Cdc2, CyclinB1 and complex of Cdc2-CyclinB1, and then abolished the G2 arrest induced by OTA. Conclusion: p38 MAPK signaling pathway was involved in OTA-induced G2 arrest in GES-1 cells by modulating G2 phase related factors.