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Here, the synergistic anti\u2010MM effect of IL\u201033 and BTZ was verified, and the underlying mechanisms were elucidated. Bioinformatic analysis indicated that IL\u201033 expression levels were downregulated in MM, and that BTZ\u2010treated MM patients with high IL\u201033 levels had better prognosis than those with low IL\u201033 levels. Moreover, the patients with high IL\u201033 levels had a better treatment response to BTZ. Further immune analysis suggested that IL\u201033 can enhance the anti\u2010MM immunity. IL\u201033 and BTZ synergistically inhibited proliferation and induced apoptosis of MM cells, which was mediated by the excessive accumulation of cellular reactive oxygen species (ROS). Furthermore, increased ROS hindered the nuclear translocation of NF\u2010\u03baB\u2010p65, thereby decreasing the transcription of target stemness\u2010related genes (<jats:italic>SOX2<\/jats:italic>, <jats:italic>MYC<\/jats:italic>, and <jats:italic>OCT3\/4<\/jats:italic>). These effects induced by the combination therapy could be reversed by eliminating ROS by <jats:italic>N<\/jats:italic>\u2010acetylcysteine. In conclusion, our results indicated that IL\u201033 enhanced the sensitivity of MM to BTZ through ROS\u2010mediated inhibition of nuclear factor kappa\u2010B (NF\u2010\u03baB) signal and stemness properties.<\/jats:p>","DOI":"10.1002\/mco2.562","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T06:54:15Z","timestamp":1715324055000},"source":"Crossref","is-referenced-by-count":10,"title":["Interleukin\u201033 increases the sensitivity of multiple myeloma cells to the proteasome inhibitor bortezomib through reactive oxygen species\u2010mediated inhibition of nuclear factor kappa\u2010B signal and stemness properties"],"prefix":"10.1002","volume":"5","author":[{"given":"Ruonan","family":"Shao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou PR 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