Combination of nilotinib, but not imatinib, with doxorubicin (DXR) displayed a synergistic effect on growth inhibition and apoptosis in synovial sarcoma SW982 cells.

<p>A) Antiproliferative effect of nilotinib as single compound or combined with DXR. Synovial sarcoma cells were treated with vehicle or nilotinib (0.1–40 µM) alone or combined simultaneously with DXR (0.1, 0.3 and 0.5 µM) for 72 h. Each value represents mean ± SEM of four individual experiments performed in triplicate. B) Subsequent isobolographic analyses were performed as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037735#s2" target="_blank">Material and Methods</a> section. Drug combination was synergistic at all concentrations (CI<1), as shown in the isobologram. C) Apoptotic effect of nilotinib as single compound or combined with DXR (0.1 µM) for 72 h. <i>Upper panels</i> show the immunoreactive bands of procaspase 3, cleaved caspase 3 and PARP fragmentation in representative immunoblots. DNA content of cells was measured by flow cytometry. Columns show percentage of apoptotic cells in the absence (vehicle, V) or presence of DXR and nilotinib as single compounds or combined (DXR+nilotinib). Each column represents mean ± SEM of four independent experiments. ^***<i>P</i><0.001 versus DXR-treated cells. D) Antiproliferative effect of imatinib (0.5–10 µM) as single compound or combined with DXR (0.1 µM) for 72 h. Each column represents mean ± SEM of three independent experiments.