Department of Applied Biological Science, Tokyo Noko University, Fuchu, Tokyo, 183-8509, Japan,
Cytotechnology. 2003 Nov;43(1-3):121-6. doi: 10.1023/b:cyto.0000039902.00952.dc.
We have already reported that exogenously added reactive oxygen species (ROS) could potentiate the invasive activity of rat hepatoma cell line of AH109A by activating autocrine loop of hepatocyte growth factor (HGF)-c-Met pathway. In this report, we examined the involvement of endogenous ROS in the invasive activity of hepatoma cells by using a cell-permeable antioxidant, N-acetyl-L-cysteine (NAC). NAC could certainly scavenge intracellular ROS when directly added to the media at the concentration of 1 or 5 mM and could significantly suppress hepatoma cell invasion, although it showed a little effect on hepatoma cell proliferation at these concentrations. NAC also decreased the content of HGF mRNA and the secretion of HGF at these concentrations, leading to suppression of their invasion. In the present study, blockade of endogenous ROS by NAC proved to efficiently suppress the invasive activity of hepatoma cells by down-regulating HGF gene expression, suggesting the importance of endogenous ROS in cellular signaling of tumor cell invasion.
我们已经报道过，外源性活性氧（ROS）可以通过激活肝细胞生长因子（HGF）-c-Met 途径的自分泌环，增强大鼠肝癌细胞系 AH109A 的侵袭活性。在本报告中，我们通过使用细胞通透性抗氧化剂 N-乙酰-L-半胱氨酸（NAC），研究了内源性 ROS 在肝癌细胞侵袭活性中的作用。当以 1 或 5mM 的浓度直接添加到培养基中时，NAC 可以有效地清除细胞内的 ROS，并且可以显著抑制肝癌细胞的侵袭，尽管在这些浓度下，它对肝癌细胞的增殖影响不大。NAC 还降低了这些浓度下的 HGF mRNA 含量和 HGF 的分泌，从而抑制了它们的侵袭。在本研究中，NAC 通过阻断内源性 ROS 被证明可以有效地抑制肝癌细胞的侵袭活性，下调 HGF 基因表达，提示内源性 ROS 在肿瘤细胞侵袭的细胞信号转导中具有重要作用。
