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

Xenobiotica; the fate of foreign compounds in biological systems 2026 Vol.56(1) p. 66-74

Wang H, Lu Y, Cheng S, Zhang Y, Li Y, Zhao Q, Liu L

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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 (

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APA Wang H, Lu Y, et al. (2026). l-Arginine combined with 5-fluorouracil inhibits EMT by regulating iNOS expression in hepatocellular carcinoma.. Xenobiotica; the fate of foreign compounds in biological systems, 56(1), 66-74. https://doi.org/10.1080/00498254.2025.2599958
MLA Wang H, et al.. "l-Arginine combined with 5-fluorouracil inhibits EMT by regulating iNOS expression in hepatocellular carcinoma.." Xenobiotica; the fate of foreign compounds in biological systems, vol. 56, no. 1, 2026, pp. 66-74.
PMID 41363819

Abstract

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)., 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., 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 iNOS upregulation.

MeSH Terms

Fluorouracil; Epithelial-Mesenchymal Transition; Animals; Carcinoma, Hepatocellular; Nitric Oxide Synthase Type II; Arginine; Rats; Liver Neoplasms; Cell Proliferation; Humans; Male; Cell Line, Tumor

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