Antimyeloma effect of Abx in vivo. (A) Growth inhibition of xenografted tumor and safety of Abx treatment in male, 5-week-old ICR/SCID mice subcutaneously inoculated with KMS11, a t(4;14)+ myeloma cell line. When the xenografted tumors reached 100 mm3, intraperitoneal injection of 100 mg/kg Abx in saline on days 1, 4, 8, and 11, and/or 5 mg/kg of panobinostat (Pan) in dimethyl sulfoxide on days 1, 3, 5, 8, 10, and 12, was started (n = 5 for ctrl, n = 6 for Abx, n = 6 for Pan, and n = 5 for Abx plus panobinostat). For toxicity evaluation, 100 mg/kg of Abx was injected on days 1, 3, 4, 5, 7, 8, 10, 12, 13, and 14, and/or 5 mg/kg or 20 mg/kg of Pan was injected on days 1, 3, 5, 8, 10, and 12. Tumor size, weight, and occurrence of diarrhea were observed every day. (B) Histopathologic observation of Abx-treated xenografts. Excised xenografts were stained with H&E and subjected to immunohistochemical staining with caspase-3 and LC-3B antibodies. (C) Immunohistochemical detection of autophagy markers (LC-3B and p62/SQSTM1) in Abx and Pan-treated xenografts. cPARP, poly ADP-ribose polymerase; ctrl, control; H&E, hematoxylin & eosin.
