PDT通过氧化应激增加TMZ对胶质瘤U251细胞的抑制  

Photodynamic Therapy Increases the Inhibition of Temozolomide on Glioma Cell Line U251 through Oxidative Stress

作　　者：侯魁元[1] 邓贺民[1] 刘建勇[1] 苏颖[1] 王伟君 曲艺[1] 王丹丹[1] 焦乐 HOU Kuiyuan;DENG Hemin;LIU Jianyong(Department of Neurosurgery,The First Hospital of Qiqihar,Heilongjiang 161000,China)

机构地区：[1]齐齐哈尔市第一医院神经外科,161000

出　　处：《医学研究杂志》2023年第5期148-152,171,共6页Journal of Medical Research

基　　金：黑龙江省卫生健康委员会科研项目(2019-269)。

摘　　要：目的多重耐药性(multiple drug resistance,MDR)仍在替莫唑胺(temozolomide,TMZ)治疗胶质瘤过程中不可避免的出现,成为胶质瘤预后不佳和局部侵袭复发的重要原因。本研究旨在观察光动力疗法(photodynamic therapy,PDT)是否能增加人胶质瘤细胞U251对TMZ的化疗敏感度,并深入探讨其增敏机制。方法人源胶质瘤细胞U251进行常规体外培养,根据处理方法分为5组,即对照(control)组、TMZ组、PDT组、TMZ+激光(TMZ+Laser)组和PDT+TMZ组,应用CCK-8观察U251细胞活性、Transwell小室观察细胞侵袭能力、免疫荧光观察细胞内活性氧(reactive oxygen species,ROS)及线粒体膜电位(mitochondrial membrane potential,MMP)水平,结果数据用GraphPad Prism软件统计分析。结果CCK-8实验表明在TMZ处理后8h,即产生了U251细胞对TMZ的治疗抵抗。PDT协同应用于TMZ处理8h的U251细胞后,PDT+TMZ组光密度(OD)值、侵袭细胞数量、MMP水平与control组和TMZ组比较均降低,而ROS升高,进一步分析表明,ROS和MMP水平呈负相关(r=-0.559,P<0.05)。结论PDT通过提高TMZ作用后的胶质瘤U251细胞内的ROS总量,加强了对U251细胞增殖和侵袭能力的抑制,延缓了MDR的发生。Objective Multiple drug resistance(MDR)is still inevitable in the treatment of glioma with temozolomide(TMZ),which has become an important reason for poor prognosis and local invasion and recurrence of glioma.The aim of this study was to observe whether photodynamic therapy(PDT)could increase the chemosensitivity of human glioma cell line U251 to TMZ,and to further explore its sensitization mechanism.Methods Human glioma cell line U251 was routinely cultured in vitro.According to the treatment method,U251 cells were divided into five groups:control group,TMZ group,PDT group,TMZ+Laser group,PDT+TMZ group.CCK-8 was used to observe the activity of U251 cells;a transwell chamber was used to observe the invasive ability of cells;the immunofluorescence was used to observe the levels of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP).GraphPad prism software was used to conduct statistical analysis.Results CCK-8 experiment showed that U251 cells were resistant to TMZ after TMZ treatment for 8 hours.After PDT was applied to U251 cells treated with TMZ for 8 hours,the optical density value,the number of invasive cells,and MMP level in PDT+TMZ group were lower than those in control group and TMZ group,while ROS increased.Further analysis showed that ROS and MMP levels were negatively correlated(Pearson correlation coefficient r=-0.559,P<0.05).Conclusion PDT can enhance the inhibition of proliferation and invasion of U251 glioma cells and delay the occurrence of MDR by increasing the total amount of ROS in U251glioma cells treated with TMZ.

关 键 词：光动力疗法 氧化应激 提高 替莫唑胺 细胞抑制 

分 类 号：R73[医药卫生—肿瘤]