Harmine inhibits COX-2 expression in gastric cancer cells through PTEN/Akt/MDM2 signaling pathway / 中国药理学通报

ABSTRACT

Aim To further analyze the effects of PTEN/Akt/MDM2 signaling pathway in the harmine (HM)-mediated inhibition of COX-2 expression in gastric cancer cells. Methods PTEN-siRNA, Akt-siR-NA, MDM2-siRNA were constructed and respectively transfected into SGC-7901 and MKN45 cells,and then added or not added HM for 24 h. The expression of PTEN, Akt and phosphorylated Akt ( p-Akt), MDM2 and phosphorylated MDM2 ( p-MDM2), as well as COX-2 expression was detected by Western blot. Results HM increased PTEN expression, but inhibited p-Akt,p-MDM2 and COX-2 expression in SGC-7901 and MKN45 cells. Knockdown of PTEN blocked HM-induced inhibition of Akt and MDM2 phosphorylation, as well as down-regulation of COX-2 expression. Knockdown of Akt and treatment with HM synergisti-cally inhibited p-MDM2 and COX-2 expression. Knockdown of MDM2 and treatment with HM synergis-tically inhibited COX-2 protein expression. Conclusions HM down-regulates the expression of COX-2 protein in gastric cancer cells via PTEN/Akt/MDM2 signaling pathway.