Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition
Abstract 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 eff...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-07-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-03223-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849331639149133824 |
|---|---|
| author | Xinjian Li Minghu Fan Rong Huang Keqiang Wang Hunan Huang |
| author_facet | Xinjian Li Minghu Fan Rong Huang Keqiang Wang Hunan Huang |
| author_sort | Xinjian Li |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-53e08f3e7d8f439a9495acb9dd8780cf |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-53e08f3e7d8f439a9495acb9dd8780cf2025-08-20T03:46:28ZengSpringerDiscover Oncology2730-60112025-07-0116111710.1007/s12672-025-03223-6Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transitionXinjian Li0Minghu Fan1Rong Huang2Keqiang Wang3Hunan Huang4Department of General Surgery, Yingtan People’s HospitalDepartment of General Surgery, Yingtan 184 HospitalDepartment of General Surgery, Yingtan 184 HospitalDepartment of General Surgery, Yingtan 184 HospitalDepartment of General Surgery, Yingtan 184 HospitalAbstract 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.https://doi.org/10.1007/s12672-025-03223-6LiraglutideEpithelial-mesenchymal transitionTGF-betaSmad3Colorectal cancer |
| spellingShingle | Xinjian Li Minghu Fan Rong Huang Keqiang Wang Hunan Huang Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition Discover Oncology Liraglutide Epithelial-mesenchymal transition TGF-beta Smad3 Colorectal cancer |
| title | Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition |
| title_full | Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition |
| title_fullStr | Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition |
| title_full_unstemmed | Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition |
| title_short | Liraglutide inhibits the development of colorectal cancer by regulating TGF-β/Smad3 signaling pathway and affecting epithelial-mesenchymal transition |
| title_sort | liraglutide inhibits the development of colorectal cancer by regulating tgf β smad3 signaling pathway and affecting epithelial mesenchymal transition |
| topic | Liraglutide Epithelial-mesenchymal transition TGF-beta Smad3 Colorectal cancer |
| url | https://doi.org/10.1007/s12672-025-03223-6 |
| work_keys_str_mv | AT xinjianli liraglutideinhibitsthedevelopmentofcolorectalcancerbyregulatingtgfbsmad3signalingpathwayandaffectingepithelialmesenchymaltransition AT minghufan liraglutideinhibitsthedevelopmentofcolorectalcancerbyregulatingtgfbsmad3signalingpathwayandaffectingepithelialmesenchymaltransition AT ronghuang liraglutideinhibitsthedevelopmentofcolorectalcancerbyregulatingtgfbsmad3signalingpathwayandaffectingepithelialmesenchymaltransition AT keqiangwang liraglutideinhibitsthedevelopmentofcolorectalcancerbyregulatingtgfbsmad3signalingpathwayandaffectingepithelialmesenchymaltransition AT hunanhuang liraglutideinhibitsthedevelopmentofcolorectalcancerbyregulatingtgfbsmad3signalingpathwayandaffectingepithelialmesenchymaltransition |