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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cell Growth and Division
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1480998

Hyodeoxycholic acid inhibits colorectal cancer proliferation through the FXR/EREG/EGFR axis

Provisionally accepted
Qiang Pang Qiang Pang Shansong Huang Shansong Huang Xiaodong Li Xiaodong Li Jiaqing Cao Jiaqing Cao *
  • Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China

The final, formatted version of the article will be published soon.

    The high morbidity and mortality rates of colorectal cancer (CRC) have been a public health concern globally, and the search for additional therapeutic options is imminent. Hyodeoxycholic acid (HDCA) has been receiving attention in recent years and has demonstrated potent efficacy in several diseases. Nonetheless, the antitumor effects and molecular pathways of HDCA in CRC remain largely unexplored. In this study, we investigated how HDCA influences the growth potential of CRC cells using techniques such as flow cytometry, Edu assay, CCK-8, colony formation assay, western blot analysis, and animal experiments. It was found that HDCA treatment of CRC cells was able to significantly inhibit the proliferative capacity of the cells. Furthermore, it was discovered that HDCA primarily stimulated Farnesoid X Receptor (FXR) rather than Takeda G protein-coupled receptor 5 (TGR5) to suppress CRC growth. It was also confirmed that HDCA inhibited the Epiregulin (EREG)/ Epidermal Growth Factor Receptor (EGFR) pathway by activating FXR, and a negative correlation between FXR and EREG was analyzed in CRC tissue samples. Finally, in vivo animal studies confirmed that HDCA inhibited CRC proliferation without hepatotoxicity. Our findings indicate that HDCA suppresses the EREG/EGFR signaling route by activating FXR, thereby hindering the growth of CRC cells and demonstrating a tumor-inhibiting effect in CRC. This study may provide a new therapeutic strategy to improve the prognosis of CRC.

    Keywords: colorectal cancer, Hyodeoxycholic acid, FXR, EREG, EGFR

    Received: 15 Aug 2024; Accepted: 13 Dec 2024.

    Copyright: © 2024 Pang, Huang, Li and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jiaqing Cao, Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.