TY - JOUR
T1 - WNT/β-catenin signaling inhibitor ic-2 suppresses sphere formation and sensitizes colorectal cancer cells to 5-fluorouracil
AU - Urushibara, Shoichi
AU - Tsubota, Toshiaki
AU - Asai, Ryoma
AU - Azumi, Junya
AU - Ashida, Keigo
AU - Fujiwara, Yoshiyuki
AU - Shiota, Goshi
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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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U2 - 10.21873/anticanres.11795
DO - 10.21873/anticanres.11795
M3 - Article
C2 - 28739692
AN - SCOPUS:85026246531
SN - 0250-7005
VL - 37
SP - 4085
EP - 4091
JO - Anticancer research
JF - Anticancer research
IS - 8
ER -
