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

Fig. 9. High MAT2A expression confers sensitivity to MAT2A inhibitors in ERG-negative CRPC.

Fig. 9

A Immunoblot of MAT2A in ERG positive and negative cell lines (n = 2 independent experiments). B SFA from LNCaPabl cells under treatment with the indicated concentration of AG-270 (Left) (n = 6 biological replicates for each drug concentration) or PF-9366 (Right) (n = 3 biological replicates for each drug concentration). Bottom, images of spheres at the indicated concentration. C SFA from LNCaP cells under treatment with the indicated concentration of AG-270 (Left) (n = 6 biological replicates for each drug concentration) or PF-9366 (Right) (n = 3 biological replicates for each drug concentration). Bottom, images of spheres at the indicated concentration. D SFA from 22Rv1 cells under treatment with the indicated concentration of AG-270 (Left) (n = 3 biological replicates for each drug concentration) or PF-9366 (Right) (n = 3 biological replicates for each drug concentration). Bottom, images of spheres at the indicated concentration. E Immunoblot of H3K4me2 in ERG positive and negative cell lines (n = 2 independent experiments). F Immunoblot with indicated antibodies in LNCaPabl cells after treatment with the indicated dose of AG-270. Right, densitometry analysis of the indicated markers (n = 2 independent experiments). G Schematic representation of ex-vivo SFA from dissociated patient-derived xenograft LuCaP 145.2. H Immunoblot of MAT2A in patient-derived xenograft LuCaP 145.2 (n = 2 independent experiments). I Ex-vivo SFA from dissociated LuCaP 145.2 under treatment with the indicated concentration of AG-270 (Left) (n = 3 biological replicates for each drug concentration) or PF-9366 (Right) (n = 6 biological replicates for each drug concentration). Bottom, images of spheres at the indicated concentration. J Schematic representation of organoid establishment from LuCaP 145.2 treatment with AG-270, and evaluation of NE markers. K Number and images of organoids at the indicated concentrations (n = 7 biological replicates). L Immunoblot of NE markers in LuCaP 145.2 organoids treated with AG-270. Molecular weights are expressed in kDa (n = 2 biological experiments). Scale bars indicated in all images are 50 µm except for B and I which are 100 µm. All error bars, mean ± s.d. *p < 0.05, **p < 0.01, ***p < 0.001 ****p < 0.0001. ns = no significant. One-way-ANOVA was used to test significant differences between groups in all panels, except for K where two-sided t-test was used. Panels G and J Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.