| Autor: |
Kito Y; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Kachi K; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.; Department of Gastroenterology, Gifu Prefectural Tajimi Hospital, Tajimi 507-8522, Japan., Yoshida M; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Hori Y; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Kato A; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Sahashi H; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Toyohara T; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Kuno K; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Adachi A; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Urakabe K; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan., Kataoka H; Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan. |
| Abstrakt: |
Cholangiocarcinoma (CCA) is a cancer with a poor prognosis due to difficulties in diagnosis and limited treatment options, highlighting the urgent need for new targeted therapies. In a clinical setting, we found that leukotriene levels in bile were higher than in serum. Immunohistochemical analysis of surgically resected samples also revealed that CysLT receptor 1 (CysLTR1) was more highly expressed in CCA than in normal bile duct tissue, prompting us to investigate leukotriene as a potential therapeutic target in CCA. In vitro studies using CCA cell lines expressing CysLTR1 showed that leukotriene D4, a major ligand of CysLTR1, promoted cell proliferation, with increased phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Additionally, treatment with two clinically available anti-allergic drugs-zileuton, an inhibitor of CysLT formation, and montelukast, a CysLTR1 inhibitor-had inhibitory effects on cell proliferation and migratory capacity, accompanied by the reduced phosphorylation of AKT and ERK1/2. Furthermore, the simultaneous administration of both drugs synergistically enhanced the inhibitory effect on cell proliferation. Our study suggests that use of these drugs may represent a novel approach to treat CCA through drug repositioning. |
