l -Arginine combined with 5-fluorouracil inhibits EMT by regulating iNOS expression in hepatocellular carcinoma

This study investigated the synergistic effect of l-arginine [inducible nitric oxide synthase (iNOS) substrate] combined with 5-fluorouracil (5-FU, iNOS inducer) on epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC).In vitro, the combination significantly inhibited HCC cell proliferation, invasion, migration, and upregulated iNOS. It also decreased mesenchymal markers (N-cadherin, vimentin, Snail, Slug) and increased epithelial E-cadherin.In vivo, using diethylnitrosamine-induced HCC rats, the combination group showed extensive tumour necrosis, reduced mitoses, enhanced iNOS, reduced mesenchymal markers, elevated E-cadherin, fewer pseudopodia, and increased cytoplasmic vacuolation compared to the model group.Thus, l-arginine + 5-FU synergistically inhibits HCC metastasis by suppressing EMT via iNOS upregulation.