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. 2023 Jul 9;19(11):3544–3557. doi: 10.7150/ijbs.82566

Figure 1.

Figure 1

MDM2 inhibition is synthetic lethal with PTEN deficiency in CRC cells. A. Western blotting showing no PTEN protein expression in both HCT116 and RKO PTEN-/- clones. p-AKT was detected for validating PTEN functional deletion. GAPDH, the loading control. B. Schematic illustration of the synthetic lethality screenings with the Highly Selective Inhibitor Libraries. C. log10-IC50 plot of the screening results. A log10 scale of IC50 values of the drugs against HCT116 PTEN+/+ and PTEN-/- cells was plotted. The MDM2 inhibitor is shown with red. D. Validation of the synthetic lethality between PTEN and MDM2 using MDM2 inhibitor CGM0979 (D, E), Nutlin-3 (G, J) and MDM2 siRNA (H, K) in HCT116 and RKO PTEN-isogenic cell lines. F. The cell images were respective of HCT116 PTEN+/+ and PTEN-/- cells with CGM097 treatment for 96 h. I, L Western blot analysis presented MDM2 knockdown by siRNA in HCT116 and RKO PTEN-isogenic cells. Data are presented as mean ± SD (n = 3 independent experiments), **P < 0.01 between two indicated bars (two-way ANOVA test).