Overexpression of MCT1 attenuates lenalidomide cytotoxicity in vitro and in vivo. (A-B) Cell proliferation analysis of MM1S (A) and U266 (B) cells, which were infected with lentivirus via control constructs (empty vector [EV]) or constructs to induce MCT1 or CD147 expression, treated with dimethyl sulfoxide (DMSO) or 10 µM lenalidomide for 72 h. (C) Quantification of tumor growth during lenalidomide or vehicle control treatment using caliper measurements (Ctrl, Len: n = 4 tumors). Xenograft tumors from U266 cells expressing MCT1 or the EV control. (D) Positron emission tomography (PET) images, using ¹⁸F-fluorodeoxyglucose, of representative immunocompromised NOD-SCID mice bearing xenograft tumors expressing MCT1 or the EV control. Images were taken after 7 days of respective treatment. Arrows indicate tumors. The color scale indicates the percentage of injected dose per gram (% ID/g). Bars represent 10 mm. (E) Total lesion glycolysis of tumors determined by PET-MRI on day 7 after respective treatments. (F) Representative immunohistochemical analysis of tumors derived from the mice shown in panel D, with histomorphology visualized with hematoxylin-eosin staining and expression of cleaved caspase 3 (CC-3), MCT1, and CD79a. Analysis was performed on 10 high-power fields for each stain. Bars represent 100 µm. (G) Quantification of CC-3 staining shown in panel F. Data are expressed as means ± standard deviation. n.s., not significant; *P < .05, **P < .01, by 1-sample t test or Student t test.