Fig. 6 | Nature Communications

Fig. 6

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

Fig. 6

Olaparib induces a targetable senescence-like phenotype in a TNBC cell line. a Proliferation response of MDA-MB-231 cells treated with different concentrations of Olaparib for 6 days with analysis of cell numbers every 6 h. Control = nontreated. be MDA-MB-231 cells were treated with 2.5, 5, and 10 µM Olaparib for 6 days. b Cumulative cell death was analyzed by flow cytometry. c SAβgal positive HGSOC cells were evaluated. d Analysis of 8 and 24-h EdU pulse. e Flow cytometry analysis of cell cycle populations. f Relative mRNA levels of p21, CHK2, IL-6, IL-8, or BCL-XL evaluated by real-time Q-PCR in MDA-MB-231 cells treated with 5 μM Olaparib for 3 and 6 days. The values represent the fold change expression compared to nontreated controls. g Western blot detection of Bcl-XL in MDA-MB-231 treated with 5 µM Olaparib for 3 or 6 days. Total protein stain was used as a loading control. h, i Cell proliferation curves (h) and representative images (i) of MDA-MB-231 H2B-GFP cells treated with Olaparib (2.5 µM), ABT-263 (0.25 µM), or Olaparib/ABT-263 (2.5/0.25 µM). Scale bar, 150 µm. j, k Heat map of Bliss scores (j) or Senolytic Indexes (k) for combination treatments between Olaparib at 2.5, 5, or 10 µM concentrations and different concentrations of senolytics (see Supplementary Fig. 12A) for 3 days (0–3 days), or 6 days in TNBC cells expressing H2B-GFP. Data in (a, g, h, 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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