肿瘤细胞固有活性氧水平与氧化砷促凋亡易感性的关系

Apoptotic susceptibility of the tumor cells to arsenic trioxide is associated with the inherent level of cellular reactive oxygen species

目的 :研究肿瘤细胞株固有的活性氧 (reactiveoxygenspecies,ROS)水平与肿瘤细胞对三氧化二砷 (以下简称氧化砷 )促凋亡的易感性之间的关系。方法 :用小剂量 (2 μmol/L)氧化砷作用于人白血病细胞和食管癌细胞各一对 (NB4、U937和EC/CUHK1、EC186 7) ,以证实砷剂促凋亡敏感性在NB4和U937之间的差异以及在EC/CUHK1和EC186 7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 12 3(DHR12 3)孵育细胞(DHR12 3在细胞内被ROS氧化为发出荧光的罗丹明 12 3,Rh12 3) ,通过流式细胞仪检测细胞内Rh 12 3的荧光而测得细胞内固有ROS水平。结果 :2 μmol/L氧化砷在NB4和EC/CUHK1造成明显凋亡 ,而在U937和EC186 7未造成明显凋亡。对氧化砷敏感的NB4细胞的固有活性氧水平比不敏感的U937细胞高 ,对氧化砷敏感的EC/CUHK1细胞的固有活性氧水平比不敏感的EC186 7细胞高。结论

Purpose:To explore the association of the inherent cellular level of reactive oxygen species (ROS) with the susceptibility of the tumor cells to apoptosis induced by arsenic trioxide (As 2O 3). Methods:Low concentration(2 μmol/L) of As 2O 3 was administrated to a pair of the leukemic cell lines, NB4 versus U937, and a pair of the esophageal carcinoma cell line, EC/CUHK1 versus EC1867, to confirm the difference in their susceptibility to apoptosis induced by As 2O 3. Dihydrogenrhodamine123 (DHR123), used as a ROS capture, was incubated with the cells in the absence of As 2O 3 administration. The fluorescent intensity of rhodamine123, which was the product of cellular oxidation of DHR123, was detected by flow cytometry, and ROS was thus measured. Results:For apoptosis induction by 2 μmol/L of As 2O 3 ,NB4 was more sensitive than U937,and EC/CUHK1 more sensitive than EC1867. The inherent cellular ROS level was higher in NB4 than in U937, and also higher in EC/CUHK1 than in EC1867. Conclusions:The difference in cellular ROS level is associated with the cellular susceptibility to apoptosis induction by As 2O 3.