线粒体STAT3介导的抗氧化机制促进伯基特淋巴瘤化疗多药耐药  

Mitochondrial STAT3-mediated antioxidant mechanism promotes multidrug resistance in Burkitt lymphoma chemotherapy

作　　者：曾若兰 欧阳周[1] 陈欢 潘涛 左轶朗 覃利平 李亚军[1] 肖玲[2] 周辉[1] ZENG Ruolan;OUYANG Zhou;CHEN Huan;PAN Tao;ZUO Yilang;QIN Liping;LI Yajun;XIAO Ling;ZHOU Hui(Department of Lymphoma&Hematology,Hunan Cancer Hospital,Changsha,Hunan,410013,China;Department of His-tology and Embryology,School of Basic Medical Science,Central South University,Changsha,Hunan,410013,China)

机构地区：[1]湖南省肿瘤医院淋巴瘤血液内科,湖南长沙410013 [2]中南大学基础医学院组织学与胚胎学系,湖南长沙410013

出　　处：《肿瘤药学》2021年第5期539-546,共8页Anti-Tumor Pharmacy

基　　金：湖南省卫生计生委科技计划(B20180496);湖南省社会发展领域重点研发计划(2017SK2133);湖南省科技计划(0105679005);长沙市科技计划(kq1706041)。

摘　　要：目的探讨人伯基特淋巴瘤(BL)细胞株Namalwa^■化疗多药耐药的机制。方法构建多药耐药的BL细胞株Namalwa^■作为研究模型,采用短串联重复序列法鉴定细胞,确定研究模型的可靠性。采用流式细胞仪检测Namalwa^■细胞内活性氧水平的变化;ATP法检测Namalwa^■细胞的化疗敏感性;Western blotting及免疫荧光法检测线粒体STAT3在Namalwa^■细胞及其亲本细胞中的表达水平。结果多药耐药的Namalwa^■细胞短串联重复序列鉴定结果与亲本一致,并与ATCC数据库比对100%吻合,排除了其他细胞污染。参与活性氧水平调控的线粒体pSTAT3s727在多药耐药的Namalwa^■细胞中高表达。多药耐药Namalwa^■细胞的活性氧水平低于亲本细胞。Namalwa^■细胞的化疗敏感性受细胞内活性氧水平调控,细胞内活性氧水平降低可增加化疗抗性,升高则可增加化疗敏感性。结论线粒体pSTAT3s727介导的抗氧化机制可促进BL化疗多药耐药。ObjectiveTo investigate the mechanism of multidrug resistance of the human Burkitt lymphoma(BL) cell line Namalwa^■.MethodsNamalwa^■, a multidrug-resistant BL cell line, was constructed by concentration gradient increment method, and was identified by short tandem repeat(STR) method to determine the genetic consistency of the research model. The changes of intracellular reactive oxygen species(ROS) levels were detected by flow cytometry. The chemosensitivity of Namalwa^■cell was detected by ATP method. The expression level of mitochondrial STAT3 in both Namalwa and Namalwa^■cells was determined by Western blotting and immunofluorescence methods.ResultsThe STR results of multidrug-resistant Namalwa^■cells were fully consistent with those of parental cells, and 100% consistent with the data in ATCC database. Mitochondrial pSTAT3 s727, which was involved in the regulation of ROS level, was highly expressed in multidrug-resistant Namalwa^■cells. The level of ROS in multidrug-resistant Namalwa^■cells was lower than that in the parent cells. The chemosensitivity of Namalwa^■cells was regulated by intracellular ROS level. The decreased intracellular ROS level increased drug resistance, while the increased intracellular ROS level increased drug sensitivity.ConclusionMitochondrial pSTAT3 s727-mediated antioxidant mechanism promotes multidrug resistance in Burkitt lymphoma chemotherapy.

关 键 词：线粒体STAT3 伯基特淋巴瘤 多药耐药 

分 类 号：R733.4[医药卫生—肿瘤]