Inducible Nitric Oxide Synthase (iNOS) Activity Could Be Responsible for Resistance or Sensitivity to IFN-γ-Induced Apoptosis in Several Human Hepatoma Cell Lines

Response to interferon-γ (IFN-γ)-induced apoptosis of human hepatoma cell lines (HHCLs) is variable. We analyzed this different behavior in Hep3B, Chang-liver, HepG2, and HuH7 cells. We studied (1) IFN-γ-induced apoptosis, (2) protein expression of Stat1, (3) binding of nuclear proteins to IFN-γ activated sequence (GAS), (4) mRNA and expression of proteins acting in apoptosis, and (5) HuH7 sensitivity after inducible nitric oxide synthase (iNOS) siRNA transfection. IFN-γ induced apoptosis in Hep3B and Chang-liver cells only. In all HHCLs, Stat1 protein increased. Binding of proteins and transactivation activity of GAS increased much more in HuH7. In all HHCLs, caspase activity and apoptotic proteins were not implicated in resistance or sensitivity. iNOS mRNA and protein expression increased in HuH7, disappeared in Hep3B, and remained unchanged in Chang-liver and HepG2. We compared the role of iNOS in Hep3B and HuH7. The iNOS inhibitor, L-NAME, sensitized HuH7 to IFN-γ, Hep3B/HuH7 coculture partially inhib...