Figure 1. Simvastatin administration cooperates with obesogenic diets to drive prostate cancer.

a. Schematic representation of the experimental design. 4-6 week-old prostate-specific Pten-heterozygous (Pten^pc+/-; pc+/-) mice were fed with western diet (WD) to induce obesity. At 6 months of age, mice were randomly assigned to WD or WD loaded with simvastatin (WD + SIM) and fed for 5 months, and tissues were harvested and analysed. b. Prostate lobes weights of Pten-heterozygous (Pten^pc+/-; pc+/-) mice fed with WD (n = 16) or WD + SIM (n = 11). VP, DLP, AP refer to ventral, dorsolateral and anterior prostates, respectively. c. Histopathological characterization of the prostate (Normal: no lesions; LGPIN: Low-grade prostatic intraepithelial neoplasia; HGPIN: High-grade prostatic intraepithelial neoplasia; Cancer: prostate adenocarcinoma) (WD, n = 16, WD+SIM, n = 11). d. Representative histological images of the prostate. Left, H&E (Haematoxylin-eosin) and right, Ki67 staining. WD shows non-cancerous tissue, WD+SIM shows adenocarcinoma. e. Quantification of Ki67 positive nuclei (%), indicating proliferating cells (WD, n = 5; WD SIM, n = 5). Statistical analysis: Mann-Whitney statistic test (b, e) and Chi Square test with 3 degree freedom (c). Error bars represent median with interquartile range. *p < 0.05, **p < 0.01, ***p < 0.001.