Shoichi Urushibara1,2, Toshiaki Tsubota1, Ryoma Asai1, Junya Azumi1, Keigo Ashida2, Yoshiyuki Fujiwara2, Goshi Shiota3. 1. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University Faculty of Medicine, Yonago, Japan. 2. Department of Surgery, Division of Surgical Oncology, Tottori University Faculty of Medicine, Yonago, Japan. 3. Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University Faculty of Medicine, Yonago, Japan gshiota@med.tottori-u.ac.jp.
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. Copyright
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. Copyright