HBV down-regulates PTEN expression via Nrf2/GSK3β signaling pathway.

OBJECTIVES To investigate the effect of HBV infection on PTEN expression, and to explore the possible molecular mechanisms. METHODS HepG2 cells and HepG2.2.15 cells were cultured under suitable conditions for 48 hours, and the expressions of PTEN, Nrf2 and pGSK3β in HepG2 and HepG2.2.15 cells were detected by Western blotting. After the blank plasmid (EV) and the plasmid pWXL-Nrf2 were transiently transfected into HepG2 and HepG2.2.15 cells, respectively, the HepG2 and HepG2.2.15 cells were treated with the selective inhibitor of GSK3β (25 nmol/L LiCl). After 48 h, the expressions of Nrf2, pGSK3β and PTEN in HepG2 and HepG2.2.15 cells were examined by Western blotting. RESULTS Expression of PTEN was reduced and the levels of Nrf2 and pGSK3β were increased in HepG2.2.15 cells compared with those in the HepG2 cells (all P<0.05). After transfection with pWXL-Nrf2, the protein expression of Nrf2 and pGSK3β in cells were significantly increased while the protein expression of PTEN was decreased (all P<0.05). Furthermore, LiCl treatment up-regulated the protein expression of Nrf2 and pGSK3β, and eventually suppressed the production of PTEN (all P<0.05). CONCLUSIONS HBV may down-regulate PTEN expression via Nrf2/GSK3β signaling pathway, which may provide new ideas for the targeting therapy of hepatocellular carcinoma.