Inhibition of SRC sensitizes breast cancer cells to TRAIL. (A) Western blot analysis of MB231 cell lysates treated with different concentrations of SRC inhibitor PP2 or its inactive analogue PP3 for 1 hour, probed for phospho-SRC (pSRC) and total SRC. (B) Western blot analysis of MB231 cell lysates treated with 10 μM PP2, PP3, or DMSO for 4 hours and probed for the indicated proteins. (C) Caspase-3/7 activation by pretreatment with PP2 or PP3 for 4 hours followed by the addition of DMSO (white bars) or 1,000 ng/ml of TRAIL (black bars) for 1 hour. Data are the mean ± SEM for three experiments. The comparison between PP2-treated and DMSO-treated cells was performed by using a paired, two-tailed Student's t test. (D) Cell-viability assay of MB231 cells treated with 10 μM PP2 or PP3 or DMSO for 1 hour followed by different concentrations of TRAIL treatment for 17 hours. (E) Cell viability of different breast cancer cells after pretreatment with or without 10 μM PP2 for 1 hour followed by treatment with 125 ng/ml TRAIL for 17 hours, as measured by MTS assay. Data are shown as the mean ± SEM for three experiments for each cell line, and the data were compared by using a two-tailed Student's t test. *P < 0.05, comparing the combination treatment with TRAIL alone; **P < 0.05 comparing the combination treatment with PP2 alone; and ***P < 0.05 comparing the combination treatment with the sum of the inhibition by TRAIL alone plus the inhibitor alone.