|Fas stimulation activates NF-κB in SK-Hep1 hepatocellular carcinoma cells|
Authors: Hiroshi Okano, Katsuya Shiraki, Hidekazu Inoue, Tomoyuki Kawakita, Yukiko Saitou, Naoyuki Enokimura, Norihiko Yamamoto, Kazushi Sugimoto, Kazumoto Murata, Takeshi Nakano
First Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan
The TNF-receptor family has a dual signaling pathway, including induction of apoptosis and NF-κB activation associated with cell survival. Hepatocellular carcinoma (HCC) cells express TNF-receptor family members and the signaling from these receptors induces NF-κB activation. However, the role of Fas in induction of NF-κB activation in HCC cells is not well understood. In this study, SK-Hep1, HepG2 or HLE cells were stimulated by anti-Fas agonistic antibody. Fas stimulation induced NF-κB activation in a dose-dependent manner in SK-Hep1 and HepG2 cell lines, but not in HLE cells. Anti-Fas agonistic antibody or the metabolic inhibitor, cyclo-heximide (CHX), failed to kill SK-Hep1 cells, but co-incubation with anti-Fas agonistic antibody and CHX was effective for induction of apoptosis. SK-Hep1 cell lines receiving Fas stimulation had increased viability, but the extent of cell proliferation was not dose-dependent. The observation suggests that Fas stimulation may contribute to HCC cell survival or proliferation.