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. 2020 Dec 14;13(2):e10852. doi: 10.15252/emmm.201910852

Figure 1. Inhibition of efflux pump MRP1 synergizes with APR‐246.

Figure 1

  1. Growth suppression in cancer cells after 72 h of treatment with APR‐246 +/− MRP1 inhibitor MK‐571 as shown by the WST‐1 assay (n ≥ 3, n shown in Appendix Table S1). Cross in heatmap indicates no data available.
  2. Growth suppression in human dermal fibroblasts (HDF) by WST‐1 assay after 72 h with APR‐246 +/− MK‐571 (n = 3).
  3. Mean IC50 values (µM) for APR‐246 +/− 20 μM MK‐571 of 21 cell lines. *P < 0.0001, Wilcoxon test. Each dot represents one cell line. Mean IC50 values and n shown in Appendix Table S1.
  4. ZIP synergy scores of most synergistic area sub‐grouped according to TP53 gene status for 21 cell lines. Each dot represents one cell line. Scores and n are shown in Appendix Table S1.
  5. Sub‐G1 DNA content of OVCAR‐3 cells (R248Q) after APR‐246 +/− MK‐571 treatment as assessed by propidium iodide staining at 48 h (n = 3).
  6. OVCAR‐3 cell confluency by IncuCyte® during 72 h of treatment with APR‐246 +/− MK‐571 (n = 3).
  7. Growth suppression in HCT116 WT (n = 4) and R248W cells (n = 3) after 72‐h treatment with APR‐246 +/− MRP1 inhibitor Reversan, as shown by WST‐1.
  8. Western blot analysis of MRP1 (Cell Signaling), p53 (DO‐1), and GAPDH of HCT116 WT and R248W cells 48 h after transfection with negative control siRNAs or siRNAs targeting MRP1 or p53.
  9. Growth suppression (WST‐1 assay) of HCT116 WT and R248W cells transfected with MRP1 siRNA (n ≥ 5 and n ≥ 2, respectively) after 48 h APR‐246 treatment. Indicated values are average of four individual siRNAs targeting MRP1 and two individual negative control siRNAs. Data and n of individual siRNAs are shown in Appendix Fig S1J; data are also part of Fig 7B.
  10. Western blot analysis of MRP1 (Cell Signaling), p53 (DO‐1), and GAPDH of HCT116 WT and R248W cells 72 h after transfection with empty vector (EV) and MRP1 expression vector.
  11. Growth suppression (WST‐1 assay) of HCT116 WT and R248W cells transfected with empty vector (EV) and MRP1 expression vector after 72 h APR‐246 treatment (n = 4). Data are also part of Appendix Fig S7E.

Data information: TP53 status is shown for each cell line. Data are represented as mean ± SEM. See also Fig EV1, Appendix Fig S1 and Appendix Table S1.

Source data are available online for this figure.