Fig. 1.

Obatoclax synergistically enhances TRAIL-mediated cytotoxicity in a caspase-dependent manner in human pancreatic cancer cell lines. PANC-1 (A) and BxPC-3 (B) cells were incubated with obatoclax alone and in combination with TRAIL at indicated doses in the presence or absence of the pan-caspase inhibitor, z-VAD-fmk (50 µmol/L). Drug treatments were done for 48 h at 37 °C, and cytotoxicity was assessed by the MTS assay with absorbance measured at 492 nm. Columns, mean of triplicate experiments; bars, SD. C, BxPC-3 cells were treated with a range of concentrations of obatoclax (1.25–5 µmol/L) and TRAIL (1.25–5 ng/mL) at a fixed ratio for 48 h. Cell viability was measured using the MTS assay. A combinational index was then calculated as described in Materials and Methods and plotted against the fractional effect as shown in an isobologram. Synergism between obatoclax and TRAIL is indicated by a combination index < 1.0.