Ursolic Acid Inhibiting COX-2 Expression In Gastric Cancer Cell Through ROS/AMPK/STAT3 Signal Pathway

Objective We aimed to investigate the effects of ursolic acid on the generation of reactive oxygen species(ROS), the phosphorylation of adenosine monophosphate-activated protein kinase(AMPK) and signal transducer and activator of transcription 3(STAT3), and to clarify the signal transduction pathways involved in the ursolic acid-mediated inhibition of COX-2 expression in gastric cancer cell.Methods Human gastric cancer cell line SGC-7901 was routinely cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum. Subconfluent cell cultures were treated with different concentrations of ursolic acid for 24 h. Intracellular levels of ROS were detected by fluorescent probe 2’,7’-dichlorofluorescein diacetate(DCFH-DA). The expression of AMPK and phosphorylated AMPK(p-AMPK), STAT3 and phosphorylated STAT3(p-STAT3), as well as COX-2 was detected by Western blot analysis.Results Ursolic acid dose-dependently increased intracellular ROS production and p-AMPK expression, whereas inhibited STAT3 phosphorylation and COX-2 expression in SGC-7901 cells. Antioxidant N-acetylcysteine(NAC) and AMPK inhibitor(data not shown) blocked ursolic acid-induced inhibition of STAT3 phosphorylation and downregulation of COX-2 expression.Conclusions Ursolic acid inhibits COX-2 expression in gastric cancer cells may be mediated through ROS/AMPK/STAT3 signal transduction pathway.