Aspirin promotes apoptosis of esophageal cancer cells induced by 5-FU through inhibiting β-catenin/EMT signaling pathway / 中国药理学通报

ABSTRACT

Aim To investigate the synergistic effect of aspirin and 5-fluorouracil (5-FU) on proliferation and apoptosis of esophageal carcinoma ECA109 cells and further to explore the underlying mechanisms. Methods The ECA109 cells were cultured under different concentrations of aspirin (0. 062 5, 0. 125, 0. 25, 0.5, 1, 2 g · L-1)and 5-FU (0.01, 0.02, 0.1, 0.2, 0.5, 1 mg · L-1) respectively, then the cell proliferation was detected by CCK-8 assay. After that ECA109 cells were cultured with non-toxic low-concentration of aspirin (0. 125 g · L-1) and 5-FU (0. 1 mg · L-1). Flow cytometry analysis was used to detect the apoptotic rate. Western blot was used to evaluate the expression of apoptosis-related proteins and epithelial-mesenchymal transition (EMT)-related markers. Results Aspirin or 5-FU inhibited cell proliferation in a concentration-dependent manner. 5-FU enhanced apoptosis rate in ECA109 cells, with the down-regulation of Bcl-2 protein and up-regulation of cleaved caspase-3 protein, which was strengthened by aspirin. Furthermore, the synergistic effect of aspirin obviously downregulated the expression of N-cadherin and β-catenin protein while up-regulated the expression of E-cadherin. Conclusions Low-concentrations of aspirin and 5-FU have a synergistic effect on the proliferation and apoptosis of ECA109 cells through inhibiting β-catenin/ EMT signaling pathway, which might provide reference for esophagus cancer adjuvant chemotherapy.