Quercetin enhances 5-fluorouracil-induced apoptosis in gastric cancer by down-regulating c-Jun expression / 中国病理生理杂志

ABSTRACT

AIM:To investigate the enhancing effect of quercetin on the 5-fluorouracil-induced apoptosis in gastric cancer.METHODS: MTT assay was conducted to evaluate the effect of quercetin on the 5-fluorouracil-induced death of gastric cancer cell line BGC-823.Co-immunoprecipitation and Western blot analysis were performed to detect the expression of c-Jun and Bcl-xL,phosphorylation of c-Jun,activation of caspase-9 and caspase-3,and release of cytochrome C in BGC-823 cells treated with quercetin and 5-fluorouracil.The apoptosis of BGC-823 cells treated with quercetin and 5-fluorouracil was analyzed by flow cytometry.RESULTS: Adjuvant therapy of quercetin significantly enhanced the 5-fluorouracil-induced death of BGC-823 cells.Meanwhile, quercetin decreased the half maximal inhibitory concentration (IC50)of 5-fluorouracil to BGC-823 cells.Quercetin treatment significantly inhibited the expression of c-Jun,and inhibited the 5-fluorouracil-induced phosphorylation of c-Jun and the interaction between c-Jun and activating transcription factor 2 (ATF2).Subsequently,quercetin inhibited the up-regulation of Bcl-xL induced by 5-fluorouracil in the BGC-823 cells. However,transfection with c-Jun plasmid abolished the promoting effect of quercetin on 5-fluorouracil-induced cell death. In addition, quercetin promoted 5-fluorouracil-induced release of cytochrome C from mitochondria and caspase-dependent apoptosis in BGC-823 cells.CONCLUSION:Quercetin treatment enhances 5-fluorouracil-induced mitochondrial apoptosis in BGC-823 cells through c-Jun/ATF2/Bcl-xL pathway.