Apoptosis susceptibility of tumor cells to arsenic trioxide and the inherent cellular level of reactive oxygen species  

肿瘤细胞对氧化砷促凋亡的易感性与固有活性氧水平有关

作　　者：易静[1] 高飞[1] 史桂英[1] 李慧[1] 石学耕[1] 汤雪明[1] 

机构地区：[1]上海第二医科大学细胞生物学实验室,上海,200025

出　　处：《Chinese Medical Journal》2002年第4期603-606,共4页中华医学杂志（英文版）

基　　金：国家自然科学基金，上海市教委资助项目

摘　　要：OBJECTIVE: To explore the association of inherent cellular reactive oxygen species (ROS) levels with susceptibility of the tumor cells to apoptosis induction by arsenic trioxide (As(2)O(3)). METHODS: Low concentration (2 micromol/L) of As(2)O(3) was administered to two cultured leukemic cell lines, NB4 and U937, and two esophageal carcinoma cell lines, EC1.71 (also named EC/CUHK1) and EC1867, to confirm the difference in apoptosis susceptibility of NB4 versus U937 and of EC1.71 versus EC1867. Dihydrogenrhodamine 123 (DHR123), used as a ROS capture agent, was incubated with cells in the absence of As(2)O(3). Fluorescence intensity of rhodamine 123, the product of cellular oxidation of DHR123, was detected by flow cytometry and ROS was measured. RESULTS: Low concentration of As(2)O(3) induced apoptosis was more likely to occur in NB4 and EC1.71 cells than in U937 and EC1867 cells, or NB4 was more sensitive than U937, and EC1.71 more sensitive than EC1867 to As(2)O(3). The inherent cellular ROS level is higher in NB4 than in U937, and also higher in EC1.71 than in EC1867. CONCLUSIONS: The difference in cellular ROS level is positively associated with cellular susceptibility to apoptosis induction by As(2)O(3). The inherent ROS level might be important in defining apoptotic susceptibility to As(2)O(3).目的探讨肿瘤细胞株的固有活性氧(reactive oxygen species, ROS)水平与细胞对三氧化二砷(As2O3)促凋亡的易感性之间的关系.方法用小剂量(2μmol/L)As2O3作用于人白血病细胞和食管癌细胞各一对(NB4/U937和EC1.71/EC1867),以证实砷剂促凋亡敏感性在NB4和U937之间的差异以及在EC1.71和EC1867之间的差异.然后在不加砷剂情况下,用活性氧捕获剂双氢罗丹明123(DHR123)孵育细胞(DHR123在细胞内被ROS氧化为发出荧光的罗丹明123,Rh123),通过流式细胞仪检测细胞内Rh123的荧光而测得细胞内固有ROS水平.结果 2μmol/L As2O3在NB4和EC1.71造成明显凋亡,而在U937和EC1867未造成明显凋亡.对砷剂敏感的NB4细胞的固有活性氧水平比砷剂不敏感的U937细胞高,对砷剂敏感的EC1.71细胞的固有活性氧水平比砷剂不敏感的EC1867细胞高.结论细胞固有ROS水平的差异与细胞对三氧化二砷诱导凋亡的易感性差异有关.

关 键 词：Antineoplastic Agents APOPTOSIS ARSENICALS DNA  Neoplasm Flow Cytometry Fluorescent Dyes Humans Oxides Reactive Oxygen Species Research Support  Non-U.S. Gov't Rhodamine 123 Tumor Cells  Cultured 

分 类 号：R730[医药卫生—肿瘤]