Synergistic effect of S63845 with lapatinib, trastuzumab, or docetaxel

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Fig. 3. Synergistic effect of S63845 with lapatinib, trastuzumab, or docetaxel. Synergistic effect of S63845 with lapatinib, trastuzumab, or docetaxel. (A) SK-BR-3 cells were treated with lapatinib (500 nM), trastuzumab (100 μg/ml), and docetaxel (2 nM) or left untreated in the presence of S63845 (30 nM), with or without Q-VD-OPh (QVD; 10 μM), for 72 hours before viability analysis with propidium iodide staining. Results are presented as a percentage of untreated cells and represent three to five independent experiments. Means ± SEM are shown. *P < 0.05, **P < 0.005, ***P < 0.001. (B and C) SK-BR-3 cells were treated with increasing concentrations of S63845 and docetaxel (B), or HER2-targeted therapies lapatinib (left panel) for 72 hours or trastuzumab (right panel) for 96 hours (C), and then subjected to viability assays using CellTiter-Glo followed by BLISS score analysis. BLISS synergy values are >0.0 on the vertical axis. (D) Western blot analysis of lysates from (A) showing expression of MCL-1, BCL-XL, BAK, BAX, BIM, BID, AKT, P-AKT, ERK, P-ERK, and cleaved caspase 3 (CC3). Tubulin was used as a loading control. Delphine Merino et al., Sci Transl Med 2017;9:eaam7049 Published by AAAS