Fig. 8: WRNi kills BRCA2-deficient cancer cells and retards BRCA2^−/− xenograft tumor growth in mice.

a Colony survival of WT and BRCA2^−/− DLD1 cells exposed to WRNi (left panel) or olaparib (right panel). WT and BRCA2^−/− DLD1 cells were plated on a six-well plate at 1,500/well and exposed to the indicated doses of WRNi or olaparib 4 h after cell seeding. b Line graphs showing relative colony survival of PEO1 and PEO4 cells exposed to increasing doses of WRNi (left panel) or olaparib (right panel). PEO1 and PEO4 cells were plated on a six-well plate at 1,000 cells/well and treated with the indicated doses of WRNi or olaparib 4 h after cell seeding. In a and b, cells were grown in presence of WRNi or olaparib for 12 days before colony staining. Data represent mean ± SD of three independent experiments. c Line graph showing a relative growth rate of BRCA2^−/− (upper panel) and WT (lower panel) xenograft tumors in athymic nude mice treated with either drug vehicle or NSC61745. After the tumors reached the palpable size, mice were injected intraperitoneally with either drug vehicle or NSC617145 (25 mg/kg body weight) every alternate day for a total of 14 days. Mean tumor volume ± SD (n = 6) at each time point is shown. Tumor growth inhibition (TGI) is indicated. p-values were determined using two-tailed unpaired Welch’s t-test. d and e Immunohistochemical (IHC) staining for γH2AX (d) and 53BP1 (e) expression in tissue sections obtained from vehicle or NSC617145 treated wild type and BRCA2^−/− xenograft tumors. Representative images (×40 magnification) of DAB-stained tissue sections are shown. Scale bar represents 50 µM. Box-whisker plots showing the median integrated density of DAB staining analyzed from n = 5 tumor tissue samples under each condition. Bounds of the box represent 25th–75th percentile, middle horizontal lines show the median, whiskers indicate maximum and minimum values of the dataset; p values were calculated using two-tailed unpaired t-test. Middle horizontal lines of the boxes represent the median. Source data are provided as a Source Data file.