Journal: Communications Biology
Article Title: EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients
doi: 10.1038/s42003-025-09437-2
Figure Lengend Snippet: A Schematic overview of the compound library screening strategy, showing the range of epigenetic and natural compounds tested. B Comparative drug sensitivity analysis of MEPP versus PREPP cells, identifying compounds preferentially targeting the Trp53 / Pten -deficient background. C Identification and validation of FK228 and thioguanine as ovarian cancer–selective therapeutic candidates, supported by screening across multiple human ovarian cancer cell lines. D Experimental design for in vivo drug testing: MEPP cells were implanted subcutaneously and treated intraperitoneally with vehicle, FK228, or thioguanine (top). Representative images of tumors at necropsy are shown (bottom). E , F Tumor growth inhibition by FK228 and thioguanine ( n = 8 biologically independent animals). E Tumor growth curves in each treatment group (mean ± s.e.m.). F Tumor weights at autopsy; data analyzed by one-way ANOVA with Dunnett’s multiple comparisons test. G H&E and Ki67 IHC staining of tumors treated with vehicle, FK228, or thioguanine. Scale bar, 50 μm. H TUNEL assay of tumors treated with vehicle, FK228, or thioguanine. Scale bar, 50 μm. I , J Quantification of Ki67 scores ( n = 8 biologically independent samples) ( I ) and TUNEL-positive cells ( n = 4 biologically independent biological samples) ( J ) in vehicle-, FK228-, and thioguanine-treated tumors. Data are shown in mean ± s.e.m. Statistical significance determined by one-way ANOVA with Dunnett’s multiple comparisons test. K Gene set enrichment analysis (GSEA) of MEPP tumors treated with FK228 or thioguanine using Reactome, Gene Ontology, and Hallmark gene sets. Only pathways with FDR q < 0.05 are shown; representative pathways are labeled. L Viability of PO1 organoids following 72 h exposure to FK228 or thioguanine, analyzed by one-way ANOVA with Dunnett’s multiple comparisons test ( n = 5 independent viability experiments).
Article Snippet: FK228 (1 mg kg −1 ; MCE, Cat# HY-15149), thioguanine (1.5 mg kg −1 ; MCE, Cat# HY-13765) or vehicle were administered intraperitoneally twice a week once tumors reached 50–100 mm3.
Techniques: Drug discovery, Biomarker Discovery, In Vivo, Inhibition, Immunohistochemistry, TUNEL Assay, Labeling