EtNBSe-PDT inhibited proliferation and induced autophagy of HNE-1 cells via downregulating the Wnt/β-catenin signaling pathway

摘要

Background: Increasing evidence has suggested that autophagy may play a resistant role during photodynamic therapy (PDT). The Wnt/beta-catenin pathway is tightly involved in cell proliferation and autophagy. In this study, we aimed to determine the influence of 5-Ethylamino-9-diethylaminobenzo[a]phenoselenazinium (EtNBSe) mediated PDT (EtNBSe-PDT) on autophagy, proliferation and Wnt/beta-catenin pathway in human NPC cell line (HNE-1 cells), and further explore the underlying crosstalk between them.Methods: Cell viability and proliferation was evaluated by MTT assay. Autophagy and Wnt/beta-catenin signaling pathway was analyzed by western blotting and immunofluorescence.Results: It was revealed that EtNBSe-PDT significantly impeded the viability and proliferation of HNE-1 cells. Meanwhile EtNBSe-PDT could notably induce autophagy in HNE-1 cells accompanied with the inhibition of Wnt/beta-catenin pathway. The Wnt/beta-catenin pathway activator Wnt agonist was found to partially counteract the inhibitory proliferation of HNE-1 cells and suppress the autophagy induced by EtNBSe-PDT. In addition, pretreatment with the autophagy inhibitor 3-methyladenine (3-MA) or Wnt agonist showed the potential in enhancing the cytotoxic effect of EtNBSe-PDT (cell survival from 50.71 +/- 4.16% to 24.53 +/- 4.27% and from 52.64 +/- 3.54% to 35.74 +/- 4.27% respectively).Conclusion: Taken together, this study demonstrated that EtNBSe-PDT suppressed viability and proliferation, and induced autophagy of HNE-1 cells via downregulating the Wnt/beta-catenin pathway. The autophagy further constituted the cytoprotective mechanisms involved in HNE-1 cells, which suggested that the combination of EtNBSe-PDT and autophagy inhibitors may be a promising strategy for the treatment of human NPC.