Fig. 4
Pharmacological blockade of WNT signalling is effective in molecularly heterogeneous populations of drug-resistant CRC cells. a BRAF-mutated VACO6 and JVE109 CRC cells were treated for 5 days with increasing concentrations of porcupine inhibitor LGK974 (WNT inhib.). Cell viability was assayed by the ATP assay. Data points represent means ± SD of at least three independent experiments. b JVE109 parental and resistant-derivatives cells were treated with LGK974 for 5 days. After that, active cleaved caspase-3 was detected by immunofluorescence (green). Nuclei are stained with DAPI (blue) and actin with Phalloidin (red). Scale bar: 50 μm. c JVE109 parental and resistant-derivatives cells were treated with LGK974 for 4 days. Representative confocal microscopy images showing β‐catenin distribution (red) are reported. Nuclei are stained with DAPI (blue). Scale bar: 25 μm. d WNT inhibitor LGK974 induces a strong downregulation of β‐catenin-dependent transcriptional activity of Tcf/LEF luciferase reporter construct in CRC parental and resistant-derivatives cells. Results represent means ± SD of at least two independent experiments. Single points indicate results of single experiments. ***p < 0.001 (Student’s t test)
