Fig 2: In vivo impact of senescent fibroblasts on cancer cells. (A) Group A (LoVo and LV-GALC fibroblast cells) and Group B (LoVo and LV-NC fibroblast cells) mice, tumors sizes, and green fluorescence staining were shown. Tumor volume (B) and weight data for the two groups of mice. p < 0.05 was considered statistically significant. (C) Group A (LoVo and LV-GALC fibroblast cells) and group B (LoVo and LV-NC fibroblast cells) mice tumors were stained with P16, P21, and P53 using IHC.

Fig 3: PA promotes HFD-induced insulin resistance in liver cells.a Hypothesis of the potential underlying mechanism regarding the effects of PA on the IRS/Akt signalling pathway. b Western blot analysis (and quantification) of the effects of PA (100 µM for 10 h) on insulin-stimulated p-IRS-2 and IRS2 expression in HepG2 cells. c Western blot analysis (and quantification) of the effects of PA (100 µM for 10 h) on insulin-stimulated p-IRS-1 and IRS1 expression in HepG2 cells. d Western blot analysis (and quantification) of the effects of PA (100 µM for 10 h) on insulin-stimulated p-PI3K and PI3K expression in HepG2 cells. e Western blot analysis (and quantification) of the effects of PA (100 µM for 10 h) on insulin-stimulated FOXO1 and GSK-3ß expression in HepG2 cells. f Western blot analysis (and quantification) of the effects of PA (100 µM for 10 h) on insulin-stimulated p-Akt and Akt expression in HepG2 cells. g Western blot analysis (and quantification) of the effects of co-exposure to glucose and LDR (0.5 Gy) on insulin-stimulated PI3K, NF?B, mTOR, p-mTOR, p-Akt, p-p53, and p53 expression in HepG2 cells with or without glucose and LDR (0.5 Gy) treatment. GAPDH was used as the internal reference. The data are the means ± SDs. The Mann-Whitney test or two-tailed unpaired Student’s t-test was used for statistical analyses. *p < 0.05 indicates a significant difference. Error bars indicate SEM (standard error of the mean). a was created by Ruixue Huang and the elements used was permitted by Biorender (https://biorender.com/) because Ruixue Huang is one of the registered user.

Fig 4: (A, B) Overexpression of endogenous p53 using different sgRNAs by CRISPR/Cas9-SAM; (C, D) Clone formation assays and single target multi-shot model curve fittings in USP7-knockdown LSCC cells with p53 overexpression. Data are presented as mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001.

Fig 5: Antitumor activity of ENMD-2076 in p53-mutated triple-negative breast cancer (TNBC) PDX models in vivo. (A) Effect of ENMD-2076 treatment (200 mg/kg once daily by oral gavage) in three PDX models. Tumor growth inhibition (TGI) in vivo was statistically significant in CU_TNBC_002 and CU_TNBC_005 (TGI 71.3%, ****p < 0.0001; TGI 66.1%, ***p < 0.001, respectively). Treatment with ENMD-2076 did not result in a statistically significant decrease in TGI in the CU_TNBC_004 model (TGI 37.0%, p > 0.05). The baseline molecular analysis is provided for each model, including p53 mutation and TNBC subtype using TNBCtype (20). (B) Immunofluorescence analysis of phospho-AurA (pAurA), phospho-histone H3, and DAPI control in CU_TNBC_005 and CU_004 tumors harvested from mice treated with ENMD-2076 or vehicle at the time points noted. Representative images were acquired using confocal microscopy at 60× magnification. Scale = 5 µm.