WNT/β-catenin signaling inhibitor ic-2 suppresses sphere formation and sensitizes colorectal cancer cells to 5-fluorouracil

Shoichi Urushibara, Toshiaki Tsubota, Ryoma Asai, Junya Azumi, Keigo Ashida, Yoshiyuki Fujiwara, Goshi Shiota

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4085-4091
Number of pages7
JournalAnticancer research
Volume37
Issue number8
DOIs
Publication statusPublished - 08-2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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