Prostaglandin E2 accelerates invasion by upregulating Snail in hepatocellular carcinoma cells

• DOI: 10.1007/s13277-014-1963-4
• Publication Date: 2014-04-23T16:35:31Z
• Authors: Min Zhang; Hai Zhang; Shanyu Cheng; Dengcai Zhang; Yan Xu; Xiaoming Bai; Shukai Xia; Li Zhang; Juan Ma; Mingzhan Du; Yipin Wang; Jie Wang; Meng Chen; Jing Leng
• Keywords: Prostaglandin E2 receptor

Our previous studies showed that prostaglandin E2 (PGE2) promotes hepatoma cell growth and migration, as well invasion; however, the precise mechanism remains elusive. Snail p65 protein levels were detected in human samples with hepatocellular carcinoma (HCC) by immunohistochemistry (IHC) staining. HCC lines (Huh-7 Hep3B) used for vitro experiments. PGE2/Akt/NF-κB pathway was investigated Huh-7 Hep3B cells after treatment PGE2, EP4 receptor (EP4R) agonist, Akt inhibitor, NF-κB respectively, real-time reverse transcription (RT)-PCR, Western blotting, immunofluorescence (IF) In invasion assay performed to evaluate effect of PGE2 on tumor invasiveness. Knockdown EP4R carried out through plasmid-based small interfering RNA (siRNA) approach confirm regulation EP4R. Dual luciferase reporter assess promoter activity agonist. We found higher tissues than those control agonist significantly increased expression cells. also profoundly promoted invasiveness siRNA completely blocked PGE2-induced upregulation reduced failed find EP4R-induced reversed inhibition cAMP response element-binding (CREB), a canonical downstream target Alternatively, phosphorylated EGFR both AG1478, an phosphorylation Akt. The IκB 30 min. started increase treated 4 h, translocated into nucleus. EP4R-agonist-treated Hep3B, compared group. decreased signaling inhibitor LY294002 24 h. Treatment pyrrolidine dithiocarbamate (PDTC) at 10 μM h EP4R-agonist-induced Furthermore, we obtained sequence from TRED-Promoter Database identified putative binding site TFSEARCH analysis. Subsequently, or PDTC (NF-κB antagonist) 12 could be partially abolished additional treatment. addition, together normal liver tissues. conclusion, activates Akt/NF-κB then upregulates via EP4R/EGFR promote migration These findings may help future evaluation novel chemo-preventive strategies HCC.