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. 2018 Sep 24;9(10):986. doi: 10.1038/s41419-018-1040-9

Fig. 5. Docetaxel sensitizes low MCL-1-expressing cells to BCL-xL inhibition by enhancing mitochondrial priming.

Fig. 5

a 60 μM of PUMA peptide-induced depolarization in A549 cells treated with chemotherapy drugs at their IC50 levels. A red line is placed at the 40% level to show degree of sensitivity from each treatment. b 60 μM of BAD peptide-induced depolarization in A549 cells treated with 4 nM docetaxel. c Docetaxel sensitizes A549 cells to ABT-263 treatment. A549 cells were treated with indicated chemotherapy drugs at their IC50 levels +/- ABT-263 for 72 h and flow cytometry was applied to measure cell apoptosis. There were three samples in each group. d Docetaxel enhances sensitivity of H727 cells to PUMA and BAD peptide-induced responses. H727 cells were treated with 10 nM docetaxel for 72 h and PUMA and BAD-induced responses were measured by BH3 profiling. A red line is placed at the 40% level to show degree of sensitivity from each treatment. e Docetaxel synergizes with ABT-263 on H727 cell apoptosis. H727 cells were treated with 10 nM docetaxel +/- ABT-263 for 72 h and flow cytometry was performed to measure cell apoptosis. There were three samples in each group. f Expression analysis in A549 and H727 cells after treatment with 25 nM siRNA oligos for 48 h followed by the indicated drugs for another 24 h. g Western blot analysis on PUMA expression in parental and CRISPR-Cas9 engineered A549 cells. h Cell apoptosis analysis in A549 and H727 cells treated with 25 nM siRNA oligos followed by docetaxel and ABT-263 for 72 h. There were three samples in each group. i Cell apoptosis analysis in the parental A549 and CRISPR-Cas9 engineered A549 cells treated with docetaxel and ABT-263 for 72 h. There were three samples in each group. j Expression analysis in A549 cells treated with 25 nM siRNA for 48 h followed by treatment with 4 nM docetaxel for another 24 h. k Synergistic killing of A549 cells from docetaxel combined with siBCL-xL or A-155463. A549 cells were treated with 25 nM siRNA for 48 h followed by 4 nM docetaxel treatment for 72 h (left). A549 cells were treated with 4 nM docetaxel and 100 nM A-1155463 for 72 h (right). There were three samples in each group. l No synergistic killing of A549 cells from docetaxel and ABT-199 combination treatment. A549 cells were treated with 4 nM docetaxel and 1 μM ABT-199 for 72 h. There were three samples in each group