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. 2023 Mar 20;13:4583. doi: 10.1038/s41598-023-31484-0

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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MDM2 inhibitors reduce growth of human and mouse p53^WT cells cultured as spheroids. (a) Brightfield images of HCT116 p53^+/+, MCF7 and B16-F10 p53^+/+ spheroids at start and end of treatment. (b) Growth curves of p53^WT spheroids treated with DMSO, nutlin-3a (human cells: 5 μM; mouse cells: 10 μM), navtemadlin (human cells: 1 μM; mouse cells: 2 μM), and staurosporine (human cells: 2 μM; mouse cells: 5 μM). Black scale bars = 400 µm; white scale bars = 1000 µm. (c) Brightfield images of B16-F10 p53^+/+ spheroids after 24 h treatment with DMSO, nutlin-3a and navtemadlin. (d) Brightfield images of treated HCT116 p53^−/− and B16F10 p53^−/− spheroids at start and end of treatment. (e) Growth curves of HCT116 p53^−/− and B16F10 p53^−/− spheroids treated with DMSO, nutlin-3a, navtemadlin and staurosporine. Data points represent the median value ± 95% CI (n = 6–18 spheroids/treatment) from 2 to 3 independent experiments. Statistical significance was assessed by mixed-effects ANOVA with matching followed by post-hoc Dunnett’s correction for multiple testing (unpaired, two-tailed, α = 0.05). Adjusted P values from the Dunnett’s test are indicated (*P < 0.05; **P < 0.01; ***P < 0.001).