Coadministration of BMS354825 and UCN-01 markedly suppresses tumor growth in association with a striking induction of MM-cell apoptosis in vivo. (A) NCr-nu/nu mice were subcutaneously inoculated with 107 MM.1S cells in the right rear flank. After tumors were measurable, 50 mg/kg of BMS354825 ± 0.5 mg/kg of UCN-01 were administrated daily for 14 days. Tumor size was monitored every 2 days. Values represent the means ± SD for 8 mice, and numbers indicate P values vs UCN-01 administrated alone. After the final drug dose, tumors were excised (inset). (B-C) Cryosections of the excised tumors were stained by TUNEL with 4,6-diamidino-2-phenylindole, dihydrochloride counter-staining. Fluorescent images were captured at 20×/0.50 magnification in the superficial, central, and deep regions within tumors. Arrows indicate the dermal facet of tumors. m, muscle.
