Fig. 7: Combined MEKi/PARPi enhances DNA damage and apoptotic death of MPM cells in vivo. | Cell Death Discovery

Fig. 7: Combined MEKi/PARPi enhances DNA damage and apoptotic death of MPM cells in vivo.

From: MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma

Fig. 7

A–F Growth curves (A, C, E) and tumor weights (B, D, F) of MSTO-211H and MESO-1 xenografts and a patient-derived xenograft (PDX, BE261T) treated with MEKi (trametinib), PARPi (talazoparib or olaparib), alone and in combination. Data are presented as mean ± SEM. *p < 0.05, ****p < 0.0001 by two-way ANOVA. NS non-significant. Note that the efficacy of trametinib (1 mg/kg) as monotherapy has been assessed in MESO-1 xenografts (Fig. S1F), so the vehicle was not repeated here according to the 3 R principle of animal experimentation. G–I H&E and IHC (γ-H2AX and Caspase-3) of residual tumors from MESO1 xenografts (G), with quantifications of γ-H2AX and Caspase-3 levels shown (H, I). *p < 0.05, ****p < 0.0001 by two-way ANOVA. Original overall magnification, × 50. J, K IHC staining and quantification of γH2AX (J) and cleaved Caspase 3 (K) in residual MESO-1 xenografts after being treated with PARPi, MEKi, and the combination. Four tumors/group were randomly chosen for the analysis, with the quantification of γ-H2AX (nucleus OD value) and cleaved caspase 3 (cytoplasm OD value) based on the whole tissue slide. Representative images (200x) showing the artificial intelligence-based detection of cancer cells and the stroma marked with red and blue circles, respectively, by the QuPath software implementation. ****p < 0.0001 by Welch’s t-test.

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