Inhibition of the Otub1/c-Maf axis by LanC impairs the growth of myeloma xenografts in immunodeficient mice and improves survival of immunodeficient mice. Severe combined immunodeficiency mice were injected subcutaneously with the MM cell line LP1 or RPMI-8226. When tumors were palpable, each model was randomly divided into 3 groups (n = 5 for each group), and vehicle or 3 or 6 mg/kg of LanC was administered intraperitoneally for 15 continuous days. (A-B) Tumor growth curves for the LP1 (A) or the RPMI-8226 model (B). (C-D) Dissected tumors from the LP1 (C) or RPMI-8226 model (D). (E) RPMI-8226 and KMS11 cells were injected into the tail vein of nude mice followed by treatment with LanC (6 mg/kg) on a 5-day-on 2-day-off protocol. Mice survival was monitored. (F) Bone marrow cells from mice treated with LanC or vehicle (as shown in panel E) were collected for flow cytometric analysis for GFP-expressing MM cells. (G) Total proteins were extracted from tumor tissues of the subcutaneous models, followed by IB assay against indicated antigens. **P < .01; ***P < .001. NS, not significant.