ArticleWorld journal of gastroenterology2023
γ-aminobutyric acid B2 receptor: A potential therapeutic target for cholangiocarcinoma in patients with diabetes mellitus.
Article in World journal of gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 12 citations in OpenAlex.
- Case report of stiff - person syndrome and literature review.IBRO neuroscience reports · 2026Article
- Construction of a prognostic model for nasopharyngeal carcinoma based on serum exosomal circular RNAs and analysis of immune microenvironment.Clinical and experimental medicine · 2025Article
- The Clinical Application of GLP-1RAs and GLP-1/GIP Dual Receptor Agonists Based on Pharmacological Mechanisms: A Review.Drug design, development and therapy · 2025Review
- The double role of GABAergic system in systemic tumors: an updated review.Frontiers in oncology · 2025Review
- Glucagon-like peptide 1 receptor agonist: A potential game changer for cholangiocarcinoma.World journal of gastroenterology · 2024Article
- Liraglutide exhibits potential anti-tumor effects on the progression of intrahepatic cholangiocarcinoma, in vitro and in vivo.Scientific reports · 2024Article
- Involvement of interleukin-1β in high glucose-activated proliferation of cholangiocarcinoma.Translational gastroenterology and hepatology · 2024Article
- GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer.International journal of molecular sciences · 2023Article
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe association between diabetes mellitus (DM) and the increased risk and progression of cholangiocarcinoma (CCA) has been reported with unclear underlying mechanisms. Previous studies showed that γ-aminobutyric acid (GABA) B2 receptor (GABBR2) was upregulated in CCA cells cultured in high glucose (HG) conditions. Roles of GABA receptors in CCA progression have also been studied, but their association with DM and hyperglycemia in CCA remains unclarified.
aimTo investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.
methodsCCA cells, KKU-055 and KKU-213A, were cultured in Dulbecco Modified Eagle's Medium supplemented with 5.6 mmol/L (normal glucose, NG) or 25 mmol/L (HG) glucose and assigned as NG and HG cells, respectively. GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot. Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence. GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry, and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis. Effects of baclofen, a GABA-B receptor agonist, on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays. Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment, and the candidate signaling molecules were validated using the public transcriptomic data and western blot.
resultsGABBR2 expression in CCA cells was induced by HG in a dose- and time-dependent manner. CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia (
conclusionGABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.
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