In vivo efficacy of IC488743 treatment of human MM xenografts in SCID mice. (A) Mice injected with 5 × 106 LB cells were treated orally twice a day with control vehicle (●), and IC488743 10 mg/kg (□) or 30 mg/kg (○). Mean tumor volume was calculated as in “Murine xenograft models of human MM.” Error bars represent SD. (B) Representative whole-body images from a mouse treated for 12 days with control vehicle (top panel) or IC488743 (30 mg/kg; bottom panel). (C) Tumors harvested from IC488743 (30 mg/kg) treated mouse (right panel) and control mouse (left panel) were subjected to immunohistochemical analysis using CD31 and P-AKT Abs. CD31 and P-AKT positive cells are dark brown. (D) Mice were treated with IC488743 10 mg/kg (hyphenated line), 30 mg/kg (dotted line), or control vehicle (solid line). Survival was evaluated from the first day of treatment until death using Kaplan-Meier curves. (E) Tumor tissues were harvested from mice treated with control vehicle or IC488743 (30 mg/kg). Protein levels of phosphorylated of PDK-1 and AKT (Ser473) were determined by Western blotting of cell lysates. Actin was used as a loading control. (F) Growth of INA-6 cells engrafted in human bone chips in SCID mice was monitored by serial serum measurements of shuIL-6R. Mice were treated with IC488743 10 mg/kg (□), 30 mg/kg (▵), or control vehicle (●), and shuIL-6R levels were determined weekly by ELISA. Error bars represent SD.
