Bortezomib (BTZ) is one of the most frequently used drugs in treatment of multiple myeloma (MM), but drug-resistance often occurs and limits its clinical efficacy. Annexin Al (ANXA1) is upregulated in MM, and its knockdown enhances chemosensitivity in MM. However, whether ANXAI inhibition can increase antitumor activity of BTZ in MM cells remains unknown. In the present study, Cell Counting Kit-8 (CCK-8) and colony formation assays showed that ANXA1 silencing combined with BTZ treatment led to a more significant inhibition of MM cell proliferation than each treatment alone. Cell apoptosis was dramatically promoted in MM cells following silencing of ANXAI and BTZ administration versus that in ANXAIsilenced alone or BTZ-treated alone cells, as evidenced by decreased expression of phosphorylated signal transducers and activators of transcription 3 and BCL2, and increased expression of BAX. Moreover, we demonstrated that the levels of IL-6 and IL-23 were markedly downregulated in ANXA1-silenced and BTZ-treated MM cells. Furthermore, the combination of ANXA1 knockdown and BTZ treatment distinctly suppressed tumor growth in vivo compared with BTZ treatment alone. Taken together, our results show that downregulation of ANXAI enhances antitumor activity of BTZ in MM in vitro and in vivo, indicating that ANXAI may be a promising target for enhancing the chemosensitivity of MM to BTZ. (C) 2018 Elsevier Inc. All rights reserved.