Fig. 7: GSK-J4 reduces cancer cell viability of SCCOHT orthotopically implanted in mice.
From: SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade

a Chromatogram depicting changes in SMARCA4, at the genomic DNA level, in the SCCOHTs of two patients. The alterations were biallelic, confirming the complete inactivation of SMARCA4. A normal reference DNA is also included. b Representative clonogenic assays for the indicated cells and treatments. c Percentage of viable cells of the indicated cells, measured using MTT assays, after treatment with increasing concentrations of GSK-J4 for 5 days. Lines show the number of viable cells relative to the total number at 0 h. Error bars, mean ± SD from three replicates. EC50 half-maximal effective concentration. d Western blot of the endogenous levels of the indicated proteins and cancer cells. TUBULIN, protein-loading control (48 h treatments, except 24 h in the GSK-J4 for the OVA250L cells). e Schematic representation of different models and treatments in mice developed from the OVA-250 tumour. SCCOHT small cell carcinoma of the ovary, hypercalcemic type. CDDP cisplatin. Figure schematics were generated using https://smart.servier.com/ (https://creativecommons.org/licenses/by/3.0/). f Left panel, gross pathological photographs at necropsy of the ovarian tumours that arose in mice treated with vehicle (n = 5) or GSK-J4 (n = 7). Right panels, volume and weight of each tumour. Two-sided unpaired Student’s t-test. n.s. not significant. g Representative sections of H&E staining of tumours from the group of mice treated as indicated (n = 5 in each group). Pink areas inside the tumours indicate fibrosis. Scale bars, 2.5 mm; Lower panels, magnification of the areas indicated (rectangle); scale bar, 50 µm (above) and 25 µm (below); Lower right panel, quantification of fibrotic areas. Two-sided unpaired Student’s t-test. Error bars, mean ± SD from replicates. ****P < 0.0001. h Representative immunostaining of H3K27me3 and of CASPASE-3 for OVA250X tumours treated with vehicle or GSK-J4. Scale bars, 25 µm. The quantification of the immunostaining is provided in Supplementary Table 6. A Source Data file is available for this figure.