Proteasome Inhibitor Drives an Anti-tumor Effects of Human Adenoid Cystic Carcinoma: Correlate with the Emerging Role of Nrf2/Keap1 Signaling Pathway

Abstract Background：Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. Its unique biological characteristics and complex structures contribute to its poor survival rates. Recently, proteasome inhibitors have shown to elicit satisfactory therapeutic effects in the treatment of certain solid tumors, but few studies have been implemented to investigate the effects of proteasome inhibitor therapy for ACC. Methods：In this present study, cell counting kit-8 assay and flow cytometry assay were performed to determine the effects of proteasome inhibitor (MG132) on cell viability and apoptosis. We applied western blot and immunofluorescence staining to explore the expression of Nrf2/Keap1 pathway and P62, and utilized Nrf2 inhibitor (ML385) to evaluate the role of Nrf2/Keap1 pathway in MG132 induced cell apoptosis.Results： We discovered that MG132 significantly suppressed the growth of ACC-83 cells and induced apoptosis. The application of MG132 induced the up-regulation of Nrf2/Keap1 pathway. Furthermore, inhibition of Nrf2 attenuated the therapeutic effects of MG132 for ACC.Conclusion：our results revealed that proteasome inhibitors might potentially be useful as a promising agent in cancer chemotherapy to treat ACC through activating Nrf2/Keap1 pathway.