Figure 5.

MDM2 inhibitor enhances standard-of-care in preclinical models of cervical cancer. (A-D) Cervical cancer tumor cells were exposed to radiation in the presence of an MDM2 inhibitor. (A) SiHa cells received RT (2 Gy per fraction, three times) administered from day 1 to day 5. Western blot analysis to assess p53, MDM2, and β-Actin levels, with densitometry values quantified relative to the control (day 0). (B) Colony formation assay results. (C) Heatmap showing the relative expression of MDM2 target genes, measured by RT-qPCR, in SiHa, CasKi, and C33A cell lines. (D) Percentage of apoptotic cells in SiHa, CasKi, and C33A cell lines. (E-I) TC-1 cells were implanted subcutaneously into the flank of C57BL/6 mice. Once tumors were established, mice received the MDM2 inhibitor AMG232 orally, in combination with standard-of-care therapy (radiation and cisplatin) or as monotherapy. Created in BioRender. Sandoval, T. (2025) https://BioRender.com/kup7w13 (E) groups: Vehicle, radiotherapy (RT), Cisplatin, standard-of-care radiotherapy combined with cisplatin (SOC), MDM2 inhibitor (MDM2_inh), standard-of-care combined with MDM2 inhibitor (SOC+ MDM2_inh) (F) t-SNE plot of flow cytometry data showing identified populations and (G) density plots for each treatment group. (H) Percentage of immune cells across treatments. One-way ANOVA with multiple comparisons; exact significant p-values are shown. (I) Tumor growth kinetics, with each line representing an individual mouse. (J) Area under the curve (AUC) analysis, with each dot representing an individual mouse. One-way ANOVA with multiple comparisons; exact significant p-values are shown (D, H and J).