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. 2024 Aug 6;15:6672. doi: 10.1038/s41467-024-50908-7

Fig. 8. Pharmacological inhibition of MAT2A alone and in combination significantly reverse malignant phenotype and restore drug sensitivity in ERG/PTEN preclinical models.

Fig. 8

A Schematic representation of 3D organoid formation assay, starting from ERG/PTEN mouse prostates. B Organoids formation from dissociated prostates of ERG/PTEN mice under treatment with the indicated concentration of PF-9366 and MDV-3100, alone and in combination (n = 3 biological replicates). Right, images of organoids at the indicated concentrations. C Organoids formation from dissociated prostates of ERG/PTEN mice under treatment with the indicated concentration of AG-270 and MDV-3100, alone and in combination (n = 4 biological replicates). Right, images of organoids at the indicated concentrations. D Organoids formation from dissociated prostates of ERG/PTEN mice under treatment with the indicated concentrations of PF-9366 and GSK-343, alone and in combination (n = 4 biological replicates). Right, images of organoids at the indicated concentrations. E Organoids formation from dissociated prostates of ERG/PTEN mice under treatment with the indicated concentrations of AG-270 and GSK-343, alone and in combination (n = 4 biological replicates). Right, images of organoids at the indicated concentrations. F Schematic representation of the generation of ERG/PTEN prostate-derived cell line (EPG2). G SFA assay in EPG2 cells treated with indicated concentration of PF-9366 (n = 6 biological replicates). Right, representative images are shown. H SFA assay in EPG2 cells treated with indicated concentration of AG-270. Right, representative images are shown (n = 6 biological replicates). I SFA assay in EPG2 cells treated with indicated concentration of MDV-3100 (n = 6 biological replicates). Right, representative images are shown. J SFA assay in EPG2 cells treated with indicated concentration of GSK-343 (n = 6 biological replicates). Right, representative images are shown. K SFA assay in EPG2 cells treated with indicated concentration of PF-9366 and MDV-3100, alone and in combination (n = 6 biological replicates). Right, representative images are shown. L SFA assay in EPG2 cells treated with indicated concentration of PF-9366 and GSK-343, alone and in combination (n = 6 biological replicates). Right, representative images are shown. M SFA assay in EPG2 cells treated with indicated concentration of AG-270 and MDV-3100, alone and in combination (n = 6 biological replicates). Right, representative images are shown. N SFA assay in EPG2 cells treated with indicated concentration of AG-270 and GSK-343, alone and in combination (n = 6 biological replicates). Right, representative images are shown. Scale bars indicated in all images are 50 µm. All error bars, mean ± s.d. *p < 0.05, **p < 0.01, ***p < 0.001 ****p < 0.0001, two-sided t test. ns = no significant. One-way-ANOVA was used to test significant differences between groups in all panels. Panels A and F Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.