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利拉鲁肽在体内外对肝内胆管癌的进展具有潜在的抗肿瘤作用。

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

机构信息

Cho-Kalaphruek Excellent Research Project for Medical Students, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.

出版信息

Sci Rep. 2024 Jun 14;14(1):13726. doi: 10.1038/s41598-024-64774-2.

DOI:10.1038/s41598-024-64774-2
PMID:38877189
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11178799/
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.

摘要

胰高血糖素样肽 1 受体 (GLP-1R) 激动剂是一种新兴的抗糖尿病药物，其对胆管癌 (CCA) 风险和进展的影响存在争议。本研究旨在阐明 GLP-1R 及其激动剂在肝内 CCA (iCCA) 进展中的作用。免疫组织化学研究表明，GLP-1R 在 iCCA 组织中的表达与组织学分级不良显著相关 (P = 0.027)。用 GLP-1R 激动剂 exendin-4 和利拉鲁肽处理 iCCA 细胞系 KKU-055 和 KKU-213A，评估其对增殖和迁移的影响。Exendin-4 和利拉鲁肽在体外均未影响 CCA 细胞的增殖，但利拉鲁肽显著抑制 CCA 细胞的迁移，部分通过抑制上皮-间充质转化。相反，利拉鲁肽显著减少异种移植小鼠的 CCA 肿瘤体积和重量 (P = 0.046)。GLP-1R 在体外和体内 CCA 细胞用利拉鲁肽处理时似乎下调。此外，利拉鲁肽治疗显著抑制 CCA 细胞中的 Akt 和 STAT3 信号通路，降低其磷酸化水平。这些结果表明，利拉鲁肽可能减缓 CCA 的进展，进一步的临床研究将有益于糖尿病合并 CCA 的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/c371582bdb30/41598_2024_64774_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/138cb96af794/41598_2024_64774_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/a7a20f240983/41598_2024_64774_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/8e1d1c0d3702/41598_2024_64774_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/450d2c08cb5d/41598_2024_64774_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/ca4028f24871/41598_2024_64774_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/c371582bdb30/41598_2024_64774_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/138cb96af794/41598_2024_64774_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/a7a20f240983/41598_2024_64774_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/8e1d1c0d3702/41598_2024_64774_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/450d2c08cb5d/41598_2024_64774_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/ca4028f24871/41598_2024_64774_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e16/11178799/c371582bdb30/41598_2024_64774_Fig6_HTML.jpg

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