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  • Title: WNT/β-Catenin Signaling Inhibitor IC-2 Suppresses Sphere Formation and Sensitizes Colorectal Cancer Cells to 5-Fluorouracil.
    Author: Urushibara S, Tsubota T, Asai R, Azumi J, Ashida K, Fujiwara Y, Shiota G.
    Journal: Anticancer Res; 2017 Aug; 37(8):4085-4091. PubMed ID: 28739692.
    Abstract:
    BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most malignant types of cancer worldwide. Recent studies suggest that a small subpopulation of cells, so-called cancer stem cells (CSCs), promote the high metastasis and relapse associated with CRC. WNT/β-catenin signaling plays a critical role in CSC maintenance. Therefore, its inhibitor may suppress CSCs and improve therapeutic effects on CRC. MATERIALS AND METHODS: The effects of a derivative of WNT/β-catenin signaling inhibitor, IC-2, which we recently developed, on the CRC cell line DLD-1, were examined by luciferase reporter assay, WST assay, western blot, and sphere assay. RESULTS: The reporter assay showed that IC-2 reduced WNT/β-catenin transcriptional activity in DLD-1 cells. Notably, IC-2 reduced expression levels of CSC marker proteins, as well as sphere formation. In addition, IC-2 increasesd cytotoxicity of 5-fluorouracil (5-FU) in DLD-1 cells. CONCLUSION: These results suggest that the combination treatment of IC-2 and 5-FU can stimulate tumor-suppressive effects on CRC.
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