| Background:Previous study has found that ursolic acid(UA)inhibited the proliferation of gastric cancer cells by down-regulation of cyclooxygenase-2(COX-2)expression.However,further studies are required to elucidate the molecular mechanism by which UA inhibits COX-2 expression in gastric cancer cells.Aims:To further clarify the role of adenosine monophosphate-activated protein kinase(AMPK)/signal transducer and activator of transcription 3(STAT3)/cyclooxygenase-2(COX-2)signaling pathway in the UA-mediated inhibition of cell proliferation in gastric cancer.Methods:Human gastric cancer cell lines SGC-7901 and MKN-45 were routinely cultured in RPMI-1640(Roswell Park Memorial Institute-1640)medium with 10%heat-inactivated fetal bovine serum.The cells in logarithmic growth phase were cultured with different concentrations of ursolic acid for 24h,or treated with ursolic acid at 30 ?mol/L for the indicated time points.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;then SGC-7901 and MKN-45 cells were treated with knockdown or overexpression of AMPK or STAT3.The expression of STAT3 and phosphorylated STAT3(p-STAT3),as well as COX-2 expression was detected by Western blot analysis,and cell proliferation was detected by CCK-8 assay.Results:UA dose-and time-dependently increased p-AMPK expression,whereas inhibited p-STAT3 and COX-2 expression in SGC-7901 and MKN-45 cells.Knockdown of AMPK blocked UA-induced inhibition of STAT3 phosphorylation and downregulation of COX-2 expression.Overexpression of STAT3 blocked UA-induced downregulation of COX-2 expression.Knockdown of AMPK and overexpression of STAT3 blocked UA-induced inhibition of proliferation in gastric cancer cells.Conclusion:UA inhibits cell proliferation may be mediated by down-regulation of COX-2 expression through AMPK/STAT3 signal transduction pathway in gastric cancer cells. |
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