2. Academic Validation
  3. Liraglutide exhibits potential anti-tumor effects on the progression of intrahepatic cholangiocarcinoma, in vitro and in vivo

Liraglutide exhibits potential anti-tumor effects on the progression of intrahepatic cholangiocarcinoma, in vitro and in vivo

  • Sci Rep. 2024 Jun 14;14(1):13726. doi: 10.1038/s41598-024-64774-2.
Ronnakrit Trakoonsenathong 1 2,  Waritta Kunprom 3,  Chaiwat Aphivatanasiri 3 4,  Padcharee Yueangchantuek 2,  Paslada Pimkeeree 2 5,  Supannika Sorin 2 4,  Kullanat Khawkhiaw 2 4,  Ching-Feng Chiu 6,  Seiji Okada 7,  Sopit Wongkham 2 4,  Charupong Saengboonmee 8 9 10
Affiliations

Affiliations

  • 1 Cho-Kalaphruek Excellent Research Project for Medical Students, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 2 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
  • 3 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
  • 4 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.
  • 5 Faculty of Medical Sciences, Naresuan University, Phitsanulok, Thailand.
  • 6 Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan.
  • 7 Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.
  • 8 Cho-Kalaphruek Excellent Research Project for Medical Students, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. charusa@kku.ac.th.
  • 9 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. charusa@kku.ac.th.
  • 10 Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand. charusa@kku.ac.th.
PMID: 38877189 DOI: 10.1038/s41598-024-64774-2
Abstract

Glucagon-like peptide 1 receptor (GLP-1R) agonist is an emerging anti-diabetic medication whose effects on the risk and progression of cholangiocarcinoma (CCA) are controversial. This study aimed to elucidate the roles of GLP-1R and its agonists on intrahepatic CCA (iCCA) progression. Expressions of GLP-1R in iCCA tissues investigated by immunohistochemistry showed that GLP-1R expressions were significantly associated with poor histological grading (P = 0.027). iCCA cell lines, KKU-055 and KKU-213A, were treated with exendin-4 and liraglutide, GLP-1R agonists, and their effects on proliferation and migration were assessed. Exendin-4 and liraglutide did not affect CCA cell proliferation in vitro, but liraglutide significantly suppressed the migration of CCA cells, partly by inhibiting epithelial-mesenchymal transition. In contrast, liraglutide significantly reduced CCA tumor volumes and weights in xenografted mice (P = 0.046). GLP-1R appeared downregulated when CCA cells were treated with liraglutide in vitro and in vivo. In addition, liraglutide treatment significantly suppressed Akt and STAT3 signaling in CCA cells, by reducing their phosphorylation levels. These results suggested that liraglutide potentially slows down CCA progression, and further clinical investigation would benefit the treatment of CCA with diabetes mellitus.

Keywords

Cholangiocarcinoma; Diabetes mellitus; Glucagon-like peptide 1 receptor; Liraglutide.

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