Fig. 9
From: Tailoring a novel colorectal cancer stem cell-targeted therapy by inhibiting the SMYD3/c-MYC axis

Targeting SMYD3 in patient-derived CRC-SCs to circumvent c-MYC mediated 5-FU chemoresistance. a Quantification of cell viability by CellTiter-Glo in patient-derived CRC-SCs pre-treated or not with EM127 (10 μM) for 48 h and then treated or not with 5-FU (10 μM) for 24 h. b Quantification of cell death by Trypan blue staining in patient-derived CRC-SCs treated as described in a. c Migratory ability of growth factor-starved patient-derived CRC-SCs placed in the inner chamber of transwell plates and treated or not with EM127 (10 μM) and/or 5-FU (10 μM) for 16 h. Migrating cells were fixed and counted under a fluorescence microscope. Scale bar: 100 μm. d Bar plot representation of the flow cytometry analysis of Ki67 expression in patient-derived CRC-SCs treated as described in a. e Bar plot representation of the flow cytometry analysis of annexin V staining in patient-derived CRC-SCs treated as described in a. The graph summarizes the percentage of apoptotic cells (early + late). f−h Analysis of tumors explanted from WT HCT-116 cell xenograft mice treated with EM127 (10 mg/kg daily) and/or 5-FU (25 mg/kg every 3 days) or the vehicle alone for 12 days. Tumor volume (data are expressed as means ± SD, each dot represents one mouse) (f), representative images (g), and hematoxylin and eosin (H&E) staining (h, scale bar: 100 μm). i–k Analysis of tumors explanted from patient-derived CRC-SC xenograft mice treated with EM127 (10 mg/kg daily) and/or 5-FU (25 mg/kg every 3 days) or the vehicle alone for 12 days. Tumor volume (data are expressed as means ± SD, each dot represents one mouse) (i), representative images (j), and hematoxylin and eosin (H&E) staining (k, scale bar: 200 μm). *p < 0.05 treated vs untreated; #p < 0.05 combined treatment vs corresponding single treatments. Where applicable, data are expressed as means ± SD of 3 independent experiments