Yi J, Gao F, Shi G, Li H, Wang Z, Shi X, Tang X
Department of Cell Biology, Shanghai Second Medical University, Shanghai 200025, People's Republic of China.
Apoptosis. 2002 Jun;7(3):209-15. doi: 10.1023/a:1015331229263.
Though reactive oxygen species (ROS) has been noticed to be involved in arsenic trioxide (As(2)O(3))-induced apoptosis of tumor cells, its role in apoptosis signaling remained to be elucidated. The objective of this work was to explore the association of the inherent cellular ROS level with the susceptibility of the tumor cells to apoptosis induction by As(2)O(3). Low concentration of As(2)O(3) was administered to cultured leukemic cell lines NB4, U937, HL60 and K562. The difference in apoptotic sensitivity was displayed among four cell types. ROS probes were incubated with the cells in the absence of As(2)O(3), and ROS was thus quantified relatively by flow cytometry. We manifested, in four cell types, the inherently existed difference in whole ROS quantity, and a positive correlation between the inherent ROS level and their apoptotic sensitivity to As(2)O(3). Furthermore, by interference using a ROS producer, we demonstrated that an elevation of ROS level would sensitize the cells to As(2)O(3)-induced apoptosis. The results of the present work suggested that the inherent ROS level might be determinative in tumor cells for their apoptotic susceptibility to As(2)O(3).
尽管人们已经注意到活性氧（ROS）参与三氧化二砷（As₂O₃）诱导的肿瘤细胞凋亡，但其在凋亡信号传导中的作用仍有待阐明。本研究的目的是探讨细胞内固有ROS水平与肿瘤细胞对As₂O₃诱导凋亡的敏感性之间的关系。将低浓度的As₂O₃应用于培养的白血病细胞系NB4、U937、HL60和K562。四种细胞类型之间显示出凋亡敏感性的差异。在不存在As₂O₃的情况下，将ROS探针与细胞孵育，从而通过流式细胞术相对定量ROS。我们发现，在四种细胞类型中，整体ROS数量存在固有差异，并且固有ROS水平与其对As₂O₃的凋亡敏感性之间存在正相关。此外，通过使用ROS产生剂进行干扰，我们证明ROS水平的升高会使细胞对As₂O₃诱导的凋亡敏感。本研究结果表明，固有ROS水平可能决定肿瘤细胞对As₂O₃凋亡的敏感性。
