Alhough the mechanisms involved in the MTX-induced cytotoxic effects on different hepatoma cells remain undetermined, a previous study demonstrated that MTX-induced cytotoxic effects on HepG2 cells are related to the CD95 death receptor pathway (caspase-8/-3 cascade pathway), whereas MTX-induced cytotoxic effects on Huh7 and Hep3B cells are not related to death receptor pathways (65). This evidence concerns the gene FAS and hepatocellular carcinoma.