Fig. 7
Combination therapy of UNC2025 and TSA decreases meningioma spheroid viability and proliferation. a Relative MERTK expression (RNAseq) in 2D, 3D and tissue. b-e Viability of b WHO grade 1 (n = 4) (average IC50 = 1.59 µM) and c WHO grade 2 spheroids following UNC2025 treatment (n = 5) (average IC50 = 3.82 µM) and d WHO grade 1 (n = 9) (average IC50 = 1.33 µM) and e WHO grade 2 (n = 3) (average IC50 = 1.60 µM) following TSA treatment at 72 h. Error bars indicate standard error of mean. f, g Average IC50 for f UNC2025 (p = 0.263) and g TSA (p = 0.371) in WHO grade 1 and grade 2 spheroids and for h UNC2025 (p < 0.05) and i TSA (p < 0.05) in grade 1 2D (black) and 3D (red) cultures. Patient matched samples were used. Student’s t-test; ns = not significant, *p < 0.05 j Representative bright field images of spheroids after monotherapy and combination therapy of UNC2025 and TSA at 1 µM UNC2025 and 1 µM TSA. Scale bar = 200 µm (Leica IM8). k Relative WHO grade 1 (n = 6) and l WHO grade 2 (n = 4) spheroid viability at 72 h treatment with 1 µM and 0.5 µM TSA and UNC2025 (n = 6). Each dot represents an individual sample. m Representative immunofluorescence images of Ki67 (red) in WHO grade 1 (top) (n = 4) and WHO grade 2 (bottom) (n = 6) spheroids following 72 h of mono or combination treatment with 0.5 µM TSA and 0.5 µM UNC2025. Cell nuclei are stained with DAPI (blue). Scale bar = 100 µm. (Leica confocal SP8. (n, o) Quantification of Ki67 positive cells relative to DAPI (nuclei) after combination treatment with 0.5 µM TSA and 0.5 µM UNC2025 in n WHO grade 1 (n = 4) and o WHO grade 2 (n = 6) spheroids. Data is represented as relative to vehicle-treated controls. ns = not significant, *p < 0.05, **p < 0.01, ****p < 0.0001. One-way ANOVA with Dunett’s test for multiple comparisons