XAV939 blocks Wnt/β-catenin signalling in breast cancer cells.

<p>(<b>A–B</b>) Tankyrase inhibitors, XAV939 and IWR-1-endo, attenuate TOPFLASH activity in breast cancer MDA-MB-231 cells and in colon cancer RKO cells. MDA-MB-231 and RKO cells, stably expressing the Wnt-responsive TOPFLASH/pBAR and the control Renilla Luciferase reporter were treated with XAV939 and IWR-1-endo at the indicated concentrations in serum depleted medium (0.2% FBS) followed by 4 h incubation with control or Wnt3a conditioned medium. Cells were lysed and luciferase activities were measured. Data represents the mean of three replicates +/− standard deviation. (<b>C</b>) Inhibition of TOPFLASH activity by XAV939 in MDA-MB-231 stable cells maintained in medium supplemented with different FBS concentrations. Cells were treated overnight with 5 µM 21H7 and 1 or 5 µM XAV939 in the presence of control or Wnt3a conditioned medium with 5%, 1.25% or 0.2% FBS. Promoter activity was measured by luciferase assay. Data is shown as the mean of three replicates +/− standard deviation. (<b>D</b>) XAV939 decreases expression of Wnt target genes. MDA-MB-231 and EMT6 cells were treated with 10 μM XAV939 and Wnt3a-conditioned media overnight and the expression of Wnt target genes AXIN2 and NKD1 was measured by Real-Time PCR. Relative gene expression is plotted as the average of three PCR replicates +/− the range.