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To investigate the efficacy and mechanism of arsenic trioxide (<jats:styled-content style=\"fixed-case\">ATO<\/jats:styled-content>) with BTZ in inducing apoptosis of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells, two <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cell lines, along with primary cells from <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), were used. Additionally, the <jats:styled-content style=\"fixed-case\">NOD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">SCID<\/jats:styled-content> mice xenograft model of Jeko\u20101 cells was established to study the anti\u2010<jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> mechanisms in an in vivo setting. <jats:styled-content style=\"fixed-case\">ATO<\/jats:styled-content> treatment highly improved BTZ capacity to inhibit proliferation and induce apoptosis of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> cells. Furthermore, the interaction of Noxa and Mcl\u20101 leads Bak to release from Mcl\u20101 or from Bcl\u2010xl, which could further activate Bak and Bax and then induce cell apoptosis. We also found that when lower doses of BTZ were used in combination with <jats:styled-content style=\"fixed-case\">ATO<\/jats:styled-content>, more effective proapoptotic effects in both the cell lines and the primary cells were obtained compared to the effects of BTZ used alone at higher doses. Simultaneously, the combination of these two drugs delayed the tumor growth in mice more effectively than BTZ alone. The cooperative anti\u2010<jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content> effects of this combination therapy both in vitro and in vivo strongly provided a new strategy to the clinical treatment of <jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/cam4.511","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T01:08:30Z","timestamp":1440637710000},"page":"1754-1766","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Arsenic trioxide rewires mantle cell lymphoma response to\u00a0bortezomib"],"prefix":"10.1002","volume":"4","author":[{"given":"Ling\u2010Ling","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory for Medical Genomics and Department of Hematology Shanghai Institute of Hematology Collaborative Innovation Center of Systems Biomedicine P\u00f4le Sino\u2010Fran\u00e7ais des Sciences 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