Quercetin enhances 5-fluorouracil-induced apoptosis in gastric cancer by down-regulating c-Jun expression
10.3969/j.issn.1000-4718.2018.02.003
- VernacularTitle:槲皮素通过抑制c-Jun的表达水平增强5-氟尿嘧啶对胃癌细胞凋亡的诱导活性
- Author:
Ye HUANG
1
;
Yang LIAO
;
Yang-Bing SHEN
;
Yi-Li FENG
Author Information
1. 浙江省皮肤病防治研究所药剂科
- Keywords:
Quercetin;
c-Jun;
5-fluorouracil;
BGC-823 cells;
Bcl-xL;
Apoptosis
- From:
Chinese Journal of Pathophysiology
2018;34(2):206-211
- CountryChina
- Language:Chinese
-
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.
