Fig. 5: BET inhibitors enhance the effects of BRAF/MEK inhibitors in BRAF-mutant melanoma in a human reconstruct skin tumour microenvironment.

Human skin reconstructs containing the BRAF-mutant human melanoma cell lines, either a A375 or b 1205Lu, after 2 weeks of skin differentiation/melanoma invasion and 48 h of combination treatment using BRAFi/MEKi (dabrafenib, 50 nM + trametinib, 5 nM) ± BETi (PLX51107, 2 μM). Staining: haematoxylin and eosin (H&E), and Ki-67. The dashed lines delimited melanoma invasion area and the arrows indicate melanoma cells. Scale bars: 100 µm. Magnification: ×200. c Quantification of Ki-67 staining in melanoma cells for the conditions above. Tukey’s test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, and n.s.: non-significant) d Skin reconstruct control with no melanoma cells. Scale bars: 100 µm. Magnification: ×200.