Ursolic Acid Inhibits Gastric Cancer Cells Proliferation through AMPK/STAT3/COX-2 Signaling Pathway / 胃肠病学

ABSTRACT

Background: Previous study has found that ursolic acid (UA) inhibited the proliferation of gastric cancer cells by the down-regulation of cyclooxygenase-2 (COX-2) expression.However,its molecular mechanism is not fully clear.Aims: To investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/signal transducer and activator of transcription 3 (STAT3)/COX-2 signaling pathway in UA-mediated inhibition of gastric cancer cells proliferation.Methods: AMPK-pLVX,AMPK-shRNA,STAT3-pLVX,STAT3-shRNA plasmids were constructed,and then were transfected into human gastric cancer cell lines SGC-7901 and MKN-45,respectively.Gastric cancer cells were cultured with different concentrations of UA for different times.The expressions of phosphorylated AMPK (p-AMPK),phosphorylated STAT3 (p-STAT3) and COX-2 were measured by Western blotting,and cell proliferation was detected by CCK-8 assay.Results: UA dose-and time-dependently increased p-AMPK expression,inhibited p-STAT3 and COX-2 expressions in SGC-7901 and MKN-45 cells.Knockdown of AMPK blocked UA-induced inhibition of STAT3 phosphorylation and COX-2 expression.Overexpression of STAT3 blocked UA-induced down-regulation of COX-2 expression.Knockdown of AMPK and overexpression of STAT3 blocked UA-induced inhibition of proliferation of gastric cancer cells.Conclusions: UA may inhibit the proliferation of gastric cancer cells via down-regulation of COX-2 expression through AMPK/STAT3 pathway.