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Background <p>Liraglutide, a glucagon-like peptide-1 receptor agonist commonly used in diabetes management, has shown potential anti-cancer effects across various malignancies. However, its role and underlying mechanisms in colorectal cancer (CRC) remain unclear.</p> Method <p>We investigated the effects of Liraglutide on human normal colon epithelial (NCM-460) and colorectal cancer (CRC) cells (LoVo and HCT116) using varying concentrations. Cell viability, proliferation, apoptosis, cell cycle progression, migration, invasion, and the expression of TGF-β/Smad3 and EMT-related markers were assessed. Additionally, we explored the effects of TGF-β agonists on the TGF-β/Smad3 signaling pathway. Tumor growth was evaluated in a nude mouse model.</p> Result <p>Liraglutide reduced CRC cell proliferation in a dose-dependent manner, with the high-concentration treatment (Liraglutide-H) showing the most potent effect (<i>p</i> &lt; 0.01 for Liraglutide-L, <i>p</i> &lt; 0.0001 for Liraglutide-H). High-dose Liraglutide (Liraglutide-H) promoted apoptosis and induced G1-S phase arrest (<i>p</i> &lt; 0.05). Migration and invasion of CRC cells were significantly reduced in both treatment groups (<i>p</i> &lt; 0.05), with Liraglutide-H showing the strongest inhibitory effect. Liraglutide also modulated the TGF-β/Smad3 pathway: it decreased TGF-β, p-Smad3/Smad3 and N-cadherin levels while increasing E-cadherin levels (<i>p</i> &lt; 0.05). These effects were reversed by the addition of a TGF-β agonist (<i>p</i> &lt; 0.05).</p> Conclusion <p>Liraglutide inhibits CRC progression by modulating the TGF-β/Smad3 signaling pathway, which affects EMT, cell migration, and invasion. These findings suggest a potential therapeutic role for Liraglutide in CRC treatment.</p>

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Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月18日

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  • Xinjian Li,
  • Minghu Fan,
  • Rong Huang,
  • Keqiang Wang,
  • Hunan Huang

摘要

Background

Liraglutide, a glucagon-like peptide-1 receptor agonist commonly used in diabetes management, has shown potential anti-cancer effects across various malignancies. However, its role and underlying mechanisms in colorectal cancer (CRC) remain unclear.

Method

We investigated the effects of Liraglutide on human normal colon epithelial (NCM-460) and colorectal cancer (CRC) cells (LoVo and HCT116) using varying concentrations. Cell viability, proliferation, apoptosis, cell cycle progression, migration, invasion, and the expression of TGF-β/Smad3 and EMT-related markers were assessed. Additionally, we explored the effects of TGF-β agonists on the TGF-β/Smad3 signaling pathway. Tumor growth was evaluated in a nude mouse model.

Result

Liraglutide reduced CRC cell proliferation in a dose-dependent manner, with the high-concentration treatment (Liraglutide-H) showing the most potent effect (p < 0.01 for Liraglutide-L, p < 0.0001 for Liraglutide-H). High-dose Liraglutide (Liraglutide-H) promoted apoptosis and induced G1-S phase arrest (p < 0.05). Migration and invasion of CRC cells were significantly reduced in both treatment groups (p < 0.05), with Liraglutide-H showing the strongest inhibitory effect. Liraglutide also modulated the TGF-β/Smad3 pathway: it decreased TGF-β, p-Smad3/Smad3 and N-cadherin levels while increasing E-cadherin levels (p < 0.05). These effects were reversed by the addition of a TGF-β agonist (p < 0.05).

Conclusion

Liraglutide inhibits CRC progression by modulating the TGF-β/Smad3 signaling pathway, which affects EMT, cell migration, and invasion. These findings suggest a potential therapeutic role for Liraglutide in CRC treatment.