硒化合物基于靶标TrxR抑制脑胶质瘤生长的分子机制研究  

Study on molecular mechanism of selenium compounds based on target TrxR in inhibiting the growth of brain gliomas

作　　者：郝丕达 苏冉 谢浩博 李玉花 王维清 赵晓娟 范存东 HAO Pi-da;SU Ran;XIE Hao-bo(Linyi Third People's Hospital,Linyi 276023,China)

机构地区：[1]临沂市第三人民医院,276023 [2]山东第一医科大学第二附属医院,271000

出　　处：《中国实用医药》2024年第8期172-176,共5页China Practical Medicine

基　　金：山东省医药卫生科技项目(项目编号:202302021265)项目名称:有机硒靶向调控TrxR诱导细胞凋亡的抗肿瘤机制基金项目;临沂市重点研发计划(项目编号:2023YX0008)项目名称:硒化合物基于靶标TrxR抑制脑胶质瘤生长的分子机制研究。

摘　　要：目的探讨3个有机硒化合物硒代胱氨酸(SeC)、甲基烯酸(MeSe)、硒代蛋氨酸(SeMe)经硫氧还蛋白氧化还原酶(TrxR)靶向抑制脑胶质瘤生长的分子机制。方法选择U251和U87人恶性胶质瘤细胞、癌旁组织细胞作为研究对象,将人恶性胶质瘤细胞纳入观察组,癌旁组织细胞纳入对照组,以不同浓度的硒化合物处理U251和U87人恶性胶质瘤细胞一定时间,用Western blot法检测TrxR蛋白表达变化,运用DCF-流式细胞分析技术观察硒化合物作用下细胞氧化应激活性氧(ROS)变化情况,使用原位末端凋亡法(TUNEL)技术标记细胞内断裂的DNA,观察细胞凋亡情况。比较两组TrxR蛋白的表达水平,分析SeC、MeSe、SeMe对观察组细胞活性、细胞TrxR蛋白表达水平、细胞组织中ROS表达水平的影响。结果观察组U251、U87人恶性胶质瘤细胞TrxR蛋白表达水平分别为(26.92±2.14)、(26.76±2.32)ng/ml,较对照组的(1.09±0.21)ng/ml高,差异有统计学意义(P<0.001)。随着SeC、MeSe、SeMe浓度的升高,U251和U87人恶性胶质瘤细胞活性逐渐下降。与干预前相比,经过SeC、MeSe、SeMe干预后,U251和U87人恶性胶质瘤细胞组织中TrxR蛋白表达下降,差异有统计学意义(P<0.001)。与干预前相比,经过SeC、MeSe、SeMe干预后,U251和U87人恶性胶质瘤细胞组织中ROS表达水平升高,差异有统计学意义(P<0.001)。结论硒化合物基于靶标TrxR提高ROS表达抑制脑胶质瘤生长。Objective To explore the molecular mechanism of three organic selenium compounds selenocysteine(SeC),metholenic acid(MeSe)and selenomethionine(SeMe)based on thioredoxin reductase(TrxR)target in inhibiting the growth of brain gliomas.Methods Human glioblastoma cells and para-cancerous tissue cells in U251 and U87 were studied.Human glioblastoma cells were included in the observation group and para-cancerous tissue cells in the control group.The cells were treated with different concentrations of selenium compounds for a certain period of time.Western blot assay was used to detect the changes of TrxR protein expression;DCF-flow cytometry was used to observe the changes of cellular oxidative stress reactive oxygen species(ROS)in the cells treated with selenium compounds;TdT-mediated dUTP nick-end labeling(TUNEL)technique was used to label the broken DNA and observe the apoptosis of cells.The expression levels of TrxR protein were compared between the two groups,and the effects of SeC,MeSe and SeMe on cell activity,expression level of TrxR protein and ROS expression level in cells of the observation group were analyzed.Results The TrxR protein expression levels of U251 and U87 human malignant glioma cells in the observation group were(26.92±2.14)and(26.76±2.32)ng/ml,which were higher than(1.09±0.21)ng/ml in the control group,with statistical significance(P<0.001).The activity of U251 and U87 human malignant glioma cells gradually decreased with the increase of SeC,MeSe,and SeMe concentrations.Compared with pre-intervention,after SeC,MeSe,and SeMe intervention,TrxR protein expression decreased in U251 and U87 human malignant glioma cell tissues,with statistical significance(P<0.001).Compared with pre-intervention,after SeC,MeSe,and SeMe interventions,ROS expression levels increased in U251 and U87 human malignant glioma cell tissues,with statistical significance(P<0.001).Conclusion Selenium compounds inhibit the growth of glioma by increasing ROS expression based on TrxR.

关 键 词：硒化合物 脑胶质瘤 硫氧还蛋白氧化还原酶 

分 类 号：R739.41[医药卫生—肿瘤]