Inhibiting of Wnt/βcatenin signaling pathway reduces stemness and tumorigenic potential of metastatic melanoma

Cancer stem cells are the main drivers of tumorigenesis, chemo/radio resistance and melanoma development. Wnt/βcatenin signaling pathway in addition to its role in the development of organisms plays an important role in tumorigenesis and progression of melanoma. The aim of this study was to evaluate the effect of Wnt/βcatenin inhibiting using XAV939, as a small molecule, on stemness and metastasis of metastatic melanoma. To find the IC50 of XAV939, the viability of A375 cells was assessed in different concentration of XAV939 by MTT assay. Then the stemness potential of tumor cells was evaluated using colony formation, sphere formation assays and the qRT-PCR for the expression of genes involved in the stemness in presence and absence of selected dose of XAV939. The scratch test was used to find the effect of wnt/ βcatenin inhibition on migratory potential of A375 cell. The results of this study showed that the 48 hours treatment with 10μM concentration of XAV939 did not effect on migratory potential of A375 melanoma cells, but significantly reduced about 2 times in ability of colony and sphere formation ability. Interestingly, the βcatenin gene expression over expressed 10.88 fold post treatment with XAV939. However, the expression of c-Myc and cycD1 did not change significantly. We found that pre-treatment of cells with WNT inhibitor for 96 hours dramatically decreased in colony formation potential. Conclusion: Our results indicate that XAV939, can reduce the tumor initiating potential of the metastatic melanoma. However, it is necessary for experiments to determine the bypassing pathways inside the tumor cells.