Selenite-induced Survival of HuH7 Hepatoma Cells Involves Activation of Focal Adhesion Kinase-Phosphatidylinositol 3-Kinase-Akt Pathway and Rac1 *

摘要: Abstract Selenium has been shown to sustain the growth of selected human hepatocellular carcinoma cell lines under serum-free conditions, but detailed mechanism remained undetermined. In present study, molecular mechanism(s) involving sodium selenite (Na2SO3, Se) as a survival agent were determined. Selenite not only protects HuH7 cells from serum deprivation-induced apoptosis, it also supports its long-term in (10–7 m) supplemented medium. The anti-apoptotic effect correlates with activation focal adhesion kinase and phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Using stably transfected constitutively active Akt PI3K inhibitor LY294002, selenite-induced was be PI3K-Akt-dependent. Parallel changes included significant reduction intracellular reactive oxygen species content, reversal DNA fragmentation, suppression caspase apoptosis signal-regulating 1 activities. expressing Rac1 mutant N17 (Rac1N17-HuH7) are refractory treatment. these supplement neither triggers nor proliferation. Participation this event is supported by fact that treatment drastically enhanced Rac1. exact link between treatment, activation, kinase-PI 3-kinase, however, remains characterized. mitogenic signaling mediated may involve unconventional stimuli including higher glutathione peroxidase activity transcription levels selenoprotein P. selenium-HuH7 system we have established thus provides unique tool will allow biological role regulation hepatocytes studied detail.