In vivo effects of ABT-888 and bortezomib in MM xenograft model. (A) CB-17 SCID mice were injected SC with 3 × 106 MM1S cells. After the detection of a measurable tumor, animals were treated with vehicle alone or bortezomib (0.4 mg/kg SC every Monday and Thursday) alone or ABT-888 alone (50 mg/kg by oral gavage twice per day) or the combination of bortezomib and ABT-888. Tumor volume was assessed in 2 dimensions every 2 days until the day of killing. (B) Survival was evaluated from the first day of treatment until death (Kaplan-Meier method). (C) Protein extracts from MM1S-xenografted tumors into SCID mice treated with vehicle alone (CNT), ABT-888 (ABT) 50 mg/kg by oral gavage twice daily and bortezomib (Bort) 0.4 mg/kg SC every Monday and Thursday or the combination of ABT-888 and bortezomib were subjected to SDS-PAGE, blotted with anti-PAR Ab, and reprobed with anti-actin Ab. (D) Schematic summary of the postulated mechanisms mediating effects of ABT-888 and bortezomib in MM cells.
