Inhibition of NF-κB activation by BAY 11-7821 suppresses the proliferation and inflammation of glioma cells through inducing autophagy.

Abstract

BackgroundGliomas have been known as the most common intracranial malignant tumor, and this kind of tumors cause huge amounts of mortality. The NF-κB inhibitor BAY 11-7821 has been reported as a novel approach in the immunotherapy of lung diseases. However, the functional role of BAY 11-7821 and its association with autophagy in glioma cells have not yet been reported.MethodsIn this study, 2 glioma cell lines (U87 and U251) were treated with different doses of BAY 11-7821, or combined with authphagy inhibitor, 3-MA. Afterwards, Transwell assay, CCK-8 assay, EdU staining, Western blot and immunofluorescence assay was used to detected the cell migration, invasion, vability, autophagy in U87 and U251.ResultsOur data showed that BAY 11-7821 significantly suppressed the viability, proliferation, migration, and invasion of glioma cells in a dose-dependent manner. At the molecular level, BAY 11-7821 downregulated the protein levels of p-IκBα, p-p65, NLRP3, and p62, and upregulated the protein levels of caspase 3 and Bax, as well as decreased the levels of IL-1β and IL-18. Results showed BAY 11-7821 enhanced autophagy. While, Pre-treatment with 3-MA, an autophagy inhibitor, obviously reversed the effects of BAY 11-7821 on malignant biological behaviors of glioma cell, inflammation status, and autophagy.ConclusionsIn this study, we found that BAY 11-7821 has an effective inhibitive function on malignant biological behaviors by mediating autophagy. Our findings contribute to a better understanding of BAY 11-7821 as a potential anticancer drug in glioma via activating autophagy.