title: Enhanced autophagic flux by endoplasmic reticulum stress in human hepatocellular carcinoma cells contributes to the maintenance of cell viability.
abstract: Endoplasmic reticulum (ER) stress and autophagy are important adaptive responses in eukaryotes. The aim of this study was to investigate the autophagic responses in hepatocellular carcinoma (HCC) cells under ER stress and the effect of autophagy on cell survival and death. The human HCC cell line HepG2 was stimulated with tunicamycin to induce ER stress. Cell viability was detected using the Cell Counting Kit-8. The accumulation of autophagic compartments was observed using transmission electron microscopy. The expression of ER and autophagy-related proteins was assessed by western blotting. Autophagic flux was assessed by microtubule-associated protein 1-light chain 3 (MAP1-LC3) turnover assay in the presence of chloroquine to inhibit lysosomes. HepG2 cells subjected to the ER stress presented a significant accumulation of autophagosomes and increased conversion of LC3-I to LC3-II as well as enhanced autophagic flux as detected by the LC3 turnover assay. Inhibition of autophagy with 3-methyladenine facilitated ER stress-related cell death. We conclude that ER stress enhances the autophagic flux in HepG2 cells, which may contribute to the maintenance of cell viability.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Tai
authors.initials: T
authors.lastname: Ma
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Fan
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Du
authors.forename: Chang-Hao
authors.initials: CH
authors.lastname: Wu
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Sun
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Li
mesh_terms: D001343:Autophagy / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism; D014415:Tunicamycin
chemical_list: D008869:Microtubule-Associated Proteins; D014415:Tunicamycin