Unraveling the Role of Leukotriene A4 Hydrolase in Hepatocellular Carcinoma: Implications for Targeted Therapy and Tumor Progression

Abstract

Background: Liver cancer represents a significant health burden, with hepatocellular carcinoma (HCC) accounting for most cases. Despite treatment advances, HCC prognosis remains poor, underscoring the need for a deeper understanding of its molecular mechanisms.Aim: This study explores the role of leukotriene A4 hydrolase (LTA4H) and its product, leukotriene B4 (LTB4), in HCC progression.Methods: Bioinformatic analysis was used to evaluate the expression profiles of LTA4H and LTB4 receptors, LTB4R and LTB4R2, in human HCC samples. 2D and 3D cultures of HCC cells were treated with the selective LTA4H inhibitor SC-57461A to assess cell viability, proliferation, migration, invasion, and apoptosis. In vivo studies in nude mice bearing human HCC xenografts treated with SC-57461A were performed to evaluate tumor growth and proliferation markers (PCNA and Ki-67).Results: Gene expression analysis revealed significant upregulation of LTA4H and its receptors in HCC tissues compared to healthy liver samples. 2D and 3D cultures of human HCC cells treated with SC-57461A showed reduced cell viability, migration, invasion, and proliferation and apoptosis. In mice orthotopically implanted with human HCC cells and treated with SC-57461A, tumor growth rate, size, and proliferation marker levels were markedly decreased.Conclusions: This study identifies LTA4H as a critical factor in HCC, suggesting its potential as a prognostic biomarker. The findings also highlight the promise of LTA4H inhibitors as a new approach for developing more effective treatments for liver cancer.