Figure 2

MM-121 specifically downregulates Survivin and significantly enhances paclitaxel-induced apoptosis in paclitaxel-sensitive and -resistant breast cancer cells. (A) SKBR3.neo1, SKBR3.B3.1, or SKBR3.B3.2 cells were untreated, or treated with MM-121 (10 μg/ml) for 24 or 48 h. Cells were collected and subjected to western blot analyses of Survivin, Bcl-xL, Mcl-1, or β-actin. The densitometry analyses of Survivin signals are shown underneath, and the arbitrary numbers indicate the intensities of each cell line relative to controls, defined as 1.0. (B and C) SKBR3 and SKBR3.B3.1, or SKBR3.neo1 and SKBR3.B3.2 cells were untreated, or treated with either MM-121 (10 μg/ml) or paclitaxel (3 nmol/L) alone, or their combinations for 24 h. Cells were collected (samples of SKBR3 and SKBR3.B3.1 cells were run on one gel, and samples from SKBR3.neo1 and SKBR3.B3.2 cells were run on another) and subjected to western blot analyses of poly(ADP-ribose) polymerase (PARP: F-PARP, full-length PARP; C-PARP, cleaved PARP), caspase-8 (F-Casp-8, full-length caspase-8; C-Casp-8, cleaved caspase-8), caspase-3 (F-Casp-3, full-length caspase-3; C-Casp-3, cleaved caspase-3), or β-actin (B); or a specific apoptosis ELISA (C). Bars represent SD. ^*P <0.001 and ^**P <0.003 versus single-agent treatment.