{Reference Type}: Journal Article
{Title}: Potential of Anti-Leukotriene Drugs as New Therapeutic Agents for Inhibiting Cholangiocarcinoma Progression.
{Author}: Kito Y;Kachi K;Yoshida M;Hori Y;Kato A;Sahashi H;Toyohara T;Kuno K;Adachi A;Urakabe K;Kataoka H;
{Journal}: Molecules
{Volume}: 29
{Issue}: 14
{Year}: 2024 Jul 18
{Factor}: 4.927
{DOI}: 10.3390/molecules29143379
{Abstract}: 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.