三氧化二砷诱导人脑胶质瘤细胞抑制与活性氧水平的关系

Relationship of As_2O_3-induced growth inhibition of human glioma cells and levels of ROS

目的研究三氧化二砷(As_2O_3)对人脑胶质瘤SHG44细胞活性氧浓度及60Coγ射线照射联合As_2O_3对细胞DNA损伤中的影响。方法用2,7-二氢二氯荧光素(DCFH)标记细胞内活性氧(ROS),激光共聚焦显微镜扫描检测细胞内荧光强度;用单细胞凝胶电泳法检测DNA彗星尾长及尾部DNA百分含量,比较As_2O_3、γ线照射单独及联合作用对细胞DNA的损伤程度。结果(1)As_2O_3可明显提高SHG44细胞内ROS水平,其ROS水平的改变随As2O3作用浓度的增加而升高。(2)60Coγ射线与As_2O_3联合作用诱导SHG44细胞DNA的损伤,其损伤程度随照射剂量的增加彗星尾长、尾部DNA百分比递增。两者联合作用后彗星尾长、尾部DNA百分比分别大于相应剂量的单独照射和As2O3组(P<0.01)。结论As2O3可明显抑制SHG44细胞的增殖,增强细胞的辐射敏感性,其抑制机制与诱导细胞内ROS水平提高具有相关性。

Objective To study the effects of arsenic trioxide（As2O3） on the reactire oxygen species（ROS） level and of As2O3 combined with 6^60Coγ rays on DNA damage of SHG44 human glioma cells. Methods The fluoresent probe 2, 7-dichlorefluoresin（DCFH） was used to detect intracellular levels of ROS using laser scanning confocal microscopy（LSCM）. Single cell gel electrophoresis assay （SCGF） was used to detect SHG44 cells DNA damage. The index of DNA damage tail moment and percentage of tail of the comet were used to evaluate the extent of DNA damage. Results Compared with that of control group, the intracellular ROS level was significantly elevated when the cells were treated by As2O3. The DNA damage of SHG44 cells treated with ^60Coγ rays associated with As2O3 was significantly increased more than that with ^60Coγ rays or As2O3 alone（P〈0. 01）. Conclusion As2O3 could inhibit the growth of SHG44 cells and increase the radiosensitivity significantly, which might be correlated with the increase of ROS levels in the cells.