title: Inhibition of autophagy promotes cell apoptosis induced by the proteasome inhibitor MG-132 in human esophageal squamous cell carcinoma EC9706 cells.
abstract: Lysosome-dependent macroautophagy, also termed autophagy, and the ubiquitin-proteasome system and are the primary intracellular pathways involved in protein degradation. Previous studies have demonstrated that proteasome inhibitors are able to inhibit tumor growth and activate autophagy. The present study investigated the effect of the proteasome inhibitor MG-132 on cellular proliferation using a cell counting kit 8 assay, and the effect of the agent on apoptosis and autophagy was assessed using flow cytometry and monodansylcadaverine, respectively. Western blot analysis was used to investigate protein changes during the course of treatment. It was revealed that MG-132 inhibited cell proliferation, activated autophagy and induced cell death in EC9706 cells. Autophagy was activated through the class III PI3K pathway, and the expression of the Beclin-1 protein was determined to be significantly upregulated. However, the autophagy inhibitor 3-methyladenine (3-MA) inhibited the expression of the autophagy-associated protein Beclin-1 and reduced the accumulation of autophagic vacuoles induced by MG-132. MG-132-induced apoptosis was enhanced by the autophagy inhibitor 3-MA, which may be a result of caspase-3 activation in the EC9706 cells. These findings suggest that inhibition of the proteasome can induce autophagy in human ESCC cells, and also increase cell death. This indicates that proteasome inhibitors may be potential novel anti-cancer agents for the adjuvant treatment of esophageal squamous cell carcinoma.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Liu
authors.affiliation: Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Qi
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
keywords: autophagy; esophageal squamous carcinoma cells; proteasome inhibitor