Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells.

摘要

OBJECTIVE: We sought to determine whether paeoniflorin enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relationship between this apoptosis and NF-kappaB activation. METHODS: Paeoniflorin was diluted to different concentrations and added to gastric carcinoma cells (SGC-7901) at different times. Western blot was used to test the expression of NF-kappaB in nuclear and I kappaB alpha, p-I kappaB alpha, IKK alpha in cytoplasm. Further, the intranuclear expression of NF-kappaB was confirmed by ELISA assay. The impact of paeoniflorin and 5-fluorouracil on cell apoptosis of gastric carcinoma cells was estimated by flow cytometry. RESULTS: Paeoniflorin revealed dramatic inhibition of NF-kappaB activity in the nuclei of the cells. The inhibition pattern of NF-kappaB was exhibited in a time- and dose-dependent manner, which was confirmed by Western blot and ELISA. Decreased nuclear translocation of NF-kappaB induced by paeoniflorin was found by preventing IkappaB alpha phosphorylation. Moreover, 5-fluorouracil-induced cell apoptosis was promoted by paeoniflorin in gastric carcinoma cells. CONCLUSIONS: Paeoniflorin can inhibit NF-kappaB activity of SGC-7901 cells, and enhance 5-fluorouracil-induced apoptosis of gastric carcinoma cells.