Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Exp Cell Res. 2010 Dec 10;316(20):3468-77. doi: 10.1016/j.yexcr.2010.07.003. Epub 2010 Jul 17.
Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.
越来越多的证据表明，血栓素合酶（TXS）的抑制可诱导癌细胞凋亡。TXS 抑制剂 1-苄基咪唑（1-BI）可引发肺癌细胞凋亡，但具体机制尚不完全清楚。本研究用 1-BI 处理肺癌细胞。本研究测定了人肺癌细胞中活性氧（ROS）的水平和 NF-κB 活性。分析了 ROS 和 NF-κB 在 1-BI 介导的细胞死亡中的作用。结果表明，1-BI 诱导 ROS 生成，但通过减少磷酸化 IκBα（p-IκBα）并抑制 p65 向核内易位来降低 NF-κB 的活性。与 1-BI 相反，抗氧化剂 N-乙酰半胱氨酸（NAC）通过中和 ROS 刺激细胞增殖，并显著保护细胞免受 1-BI 介导的细胞死亡。总之，1-BI 诱导的细胞凋亡与 ROS 的过度产生和 NF-κB 的减少有关。抗氧化剂可显著阻断 1-BI 的抑制作用。
