Jing Xu-Bin, Cai Xian-Bin, Hu Hui, Chen Su-Zuan, Chen Bin-Ming, Cai Ju-Yu
Department of Gastroenterology, The First Affiliated Hospital, Shantou University Medical College, 57 Chang Ping Road, Shantou 515041, Guangdong Province, China.
Biochem Cell Biol. 2007 Apr;85(2):265-71. doi: 10.1139/O07-014.
cis-Diamminedichloroplatinum (CDDP), commonly know as cisplatin, is a well known DNA-damaging agent, which is highly active in suppressing the proliferation of tumor cells. However, it is not clear that CDDP can induce growth inhibition of esophagus cancer cells. Using the cell line EC-109 from the esophagus, we found that CDDP would induce apoptotic responses. The addition of CDDP to cells led to the inhibition of growth in a time- and dose-dependent manner. CDDP generated reactive oxygen species (ROSs) in cells, which brought about a reduction in the intracellular mitochondrial transmembrane potential (Deltapsim), leading to apoptosis. Our findings demonstrate that ROSs, and the resulting oxidative stress, play a pivotal role in apoptosis. Preincubation of EC-109 cells with the hydrogen-peroxide-scavenging enzyme catalase partially inhibited the following: (i) the production of ROS; (ii) the disruption of the Deltapsim; and (iii) apoptosis. These results indicate that the enhancement of the generation of ROS and the disruption of Deltapsim are events involved in the apoptotic pathway of EC-109 induced by CDDP.
顺二氯二氨铂（CDDP），通常称为顺铂，是一种著名的DNA损伤剂，在抑制肿瘤细胞增殖方面具有高度活性。然而，尚不清楚CDDP是否能诱导食管癌细胞的生长抑制。使用来自食管的EC-109细胞系，我们发现CDDP会诱导凋亡反应。向细胞中添加CDDP导致生长抑制呈时间和剂量依赖性。CDDP在细胞中产生活性氧（ROS），这导致细胞内线粒体跨膜电位（Δψm）降低，从而导致凋亡。我们的研究结果表明，ROS以及由此产生的氧化应激在凋亡中起关键作用。用清除过氧化氢的酶过氧化氢酶对EC-109细胞进行预孵育可部分抑制以下情况：（i）ROS的产生；（ii）Δψm的破坏；以及（iii）凋亡。这些结果表明，ROS生成的增强和Δψm的破坏是CDDP诱导的EC-109凋亡途径中的相关事件。
