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. 2022 Sep 28;2(9):1075–1088. doi: 10.1158/2767-9764.CRC-22-0053

FIGURE 4.

FIGURE 4

Reactivation of p53 with Navtemadlin synergizes with radiotherapy. A, B16-F10+/+ Bliss synergy scores for Navtemadlin and radiation combination treatments, BLISS score was defined as >10 synergistic (red), <−10 antagonistic (green), and <10 > −10 additive (white). B, B16-F10+/+ cell growth, measured as confluence by the Incucyte S3, % inhibited by radiotherapy and Navtemadlin treatment individually. C, % of apoptotic cells in B16-F10 cells treated with a single dose of 2 Gy radiation followed by 72 hours 1.5 μmol/L Navtemadlin. Apoptosis was defined by low nuclear area and high bright-field contrast using IDEAS software. D, Representative images of apoptotic and live B16-F10 p53+/+ cells were obtained after 72 hours combination treatment, 2 Gy followed by 1.5 μmol/L Navtemadlin treatment E and F, Median fluorescence intensity (MFI) of p53, p21, PUMA and BAX in B16-F10 cells analyzed with imaging flow cytometry after a single dose of 2 Gy radiation followed by 48 or 72 hours 1.5 μmol/L Navtemadlin treatment. Data in C pooled from two experiments performed with triplicates. Data in A and B and E and F representative of two to three experiments performed with triplicates. Mean ± SD. *, P < 0.05; **, P < 0.002; ***, P < 0.0002; ****, P < 0.0001. One-way ANOVA.