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Reactive oxygen species regulate urokinase plasminogen activator expression and cell invasion via mitogen-activated protein kinase pathways after treatment with hepatocyte growth factor in stomach cancer cells

DOI: 10.1186/1756-9966-28-73

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Intracellular ROS, as determined using the fluorescent probe, 2'-7' dichlorofluorescein diacetate, decreased after treatment with hepatocyte growth factor (HGF). We confirmed that Rac-1 regulated ROS production after activation of the AKT pathway with HGF. Exogenously added H2O2 promoted the expression of HGF, but not in a dose-dependent manner and also showed negative expression of HGF after co-treatment with H2O2 and HGF. Treatment with NAC, an intracellular free radical scavenger, decreased the enhancement of uPA production and tumor invasion in both cells. We clarified the downstream pathways regulated by ROS after treatment with H2O2, which showed negative control between FRK and p38 kinase activities for uPA regulation.HGF regulates Rac-1-induced ROS production through the Akt pathway and ROS regulates uPA production and invasion via MAP kinase, which provides novel insight into the mechanisms underlying the progression of gastric cancer.Gastric cancer is the second most common cause of cancer death worldwide despite of the improved prognosis. To understand the precise mechanisms underlying invasion and metastasis would be helpful in improving survival. ROS, such as superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (HO-), have emerged as highly toxic agents responsible for a wide variety of tissue damage [1] The involvement of these ROS in the pathogenesis of gastric diseases first became evident from the study of gastric mucosal injuries under normal conditions. ROS are relatively harmless, but when produced excessively or during deficient antioxidant defense, the oxidant and antioxidant balance is disturbed and the metabolites become toxic, which may lead to the initiation and promotion of cancer [2]. However, despite the positive correlation between the increased generation of ROS and the invasion of cancer, the specific mechanisms by which antioxidants act to suppress cancer development through ROS is unknown.HGF has multiple biologic


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