Fig. 4 | Nature Communications

Fig. 4

From: Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence

Fig. 4

Olaparib and Bcl2/Bcl-XL inhibitors are synergistic. a Cell proliferation curves of OV1369(R2) H2B-GFP cell line treated with Olaparib (10 µM), ABT-263 (0.25 µM), or Olaparib/ABT-263 (10/0.25 µM) for 6 days. b, c OV1369(R2) treated for 6 days with Olaparib (10 µM), ABT-263 (0.25 µM) or the combination Olaparib/ABT-263 (10/0.25 µM). Representative images of cell morphology and cell fate. Scale bar, 150 µm (b). Representative flow cytometry analysis of apoptosis showing DRAQ7 positive cell population (X-axis) and AnnexinV positive cells (Y-axis) (c). d Percentage of dead cells for all four HGSOC cell lines treated with their respective PARPi IC50 combined to ABT-263 (0.25 µM for OV1369(R2) and 2.5 µM for the other cell lines) analyzed by flow cytometry as in (c). e, f CI values for the entire fraction affected (Fa) (e) and the mean ± SEM of the CI at Fa 0.50/0.75 (f) of HGSOC cells expressing H2B-GFP for the combined treatment (Olaparib/ABT-263) at specific drug ratios (Supplementary Fig. 6B). g Comparison of BCL2 and BCLXL mRNA expression in HGSOC according to the TCGA dataset (530 samples, cBioPortal). h Relative mRNA expression of BCL2 and BCLXL evaluated by real-time Q-PCR in HGSOC cell lines. i Western blot analyses of Bcl-XL and Bcl2 proteins in HGSOC cells treated with Olaparib for 6 days. j Heat map of Bliss scores for combination treatments between Olaparib IC50 and different concentrations of ABT-263, ABT-199, A133, or A115 (see Supplementary Fig. 6D) of HGSOC cells expressing H2B-GFP. Data in (ac, e, i) are a representation of at least three independent experiments. For all the data, the mean ± SEM of three independent experiments is shown. Data were analyzed using the two-tail Student t test. * Denotes p < 0.05, **p < 0.01, and ***p < 0.001

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