三溴丙酮酸抑制恶性转化的树突状细胞增殖的实验研究  

3-bromopyruvic acid inhibits the proliferation of malignant transformed dendritic cells

作　　者：颜苏吉 洪蕾 马加威 戴纯刚[1] 谢涛[1] 刘兵[1] 黄强[1] Yah Suji;Hong Lei;Ma Jiawei;Dai Chungang;Xie Tao;Liu Bing;Huang Qiang(Department of Neurosurgery,the Second Affiliated Hospital of Soochow University,Suzhou 215004,China)

机构地区：[1]苏州大学附属第二医院神经外科,215004 [2]南京医科大学苏州科技城医院临床医学研究所 [3]南京医科大学附属无锡第二医院重症医学科

出　　处：《中华神经外科杂志》2018年第11期1161-1165,共5页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金（81472739,81172400）

摘　　要：目的从阻滞糖代谢途径，探讨三溴丙酮酸（3-BrPA）抑制恶性转化的树突状细胞（DC）增殖的可能性。方法采用髓源性小鼠DC与人脑胶质瘤于细胞（SU3细胞株）体外共培养的方法，诱导DC恶性转化，对恶性转化的DC单克隆，培养的细胞命名为胶质瘤干细胞诱导恶性转化的DC（GSPC—MTDCs）。采用CCK-8法和细胞平板克隆形成实验检测SU3、正常DC、GSPC—MTDCs的增殖能力；采用Transwell小室侵袭实验检测细胞的侵袭能力。将GSPC—MTDCs接种于20只无荧光裸小鼠皮下，接种后11d，选取致瘤均一的10只裸鼠分为干预组和对照组，每组5只。干预组给予3-BrPA（5mg·kg^-1·d^-1）腹腔注射，对照组给予等体积的生理盐水腹腔注射，共干预24d。比较两组的致瘤情况。结果（1）GSPC—MTDCs具有永生化特征，与SU3相比，其增殖速度加快，克隆形成率明显增高[（38．1±1．9）％对比（30．2±2．7）％，P〈0．01]；Transwell小室侵袭实验显示，GSPC—MTDCs侵袭能力强于SU3[（1042±49）个对比（782±38）个，P〈0．01）]。（2）GSPC—MTDCs接种于无荧光裸小鼠皮下和尾静脉后全部致瘤。3-BrPA干预后24d，干预组和对照组肿瘤的重量分别为（1．5±0．6）g、（3．3±1．0）g，差异有统计学意义（P=0．0107）。病理学观察显示，相较于干预组，对照组细胞核异形明显、核分裂象多、血管丰富、炎症细胞浸润明显、c—myc阳性细胞比例高。结论胶质瘤干细胞具有诱导DC恶变的潜能；3-BrPA具有抑制GSPC—MTDCs增值的作用。Objective To explore the possible inhibiting effect of 3-bromopyruvic acid （3-BrPA） on proliferation of malignant transformed dendritic cells by blocking the pathway of glucose metabolism. Methods In vitro, co-cultured mice myeloid dendritic cells （DC） with human glioma stem cells （SU3） were used to induce the malignant transformation of DC. Among DC monoclonal for malignant transformation, i.e. , glioma stenr/progenitor cells induced by malignant transformation of dendritic cells （GSPC-MTDCs） , proliferative abilities of SU3, normal DC and GSPC-MTDCs were detected by CCK-8 and flat clone formation assay. Cell invasiveness was detected by Transwell chamber invasion assay. Subcutaneous inoculation of GSPC-MTDCs was performed in 20 non-fluorescent nude mice. At 11 d post inoculation, 10 nude mice with uniform tumorigenesis were divided into intervention group and control group with 5 mice in each group. The intervention group was given 3-BrPA （5 mg · kg^-1 · d ^-1） intraperitoneal treatment, while the control group was given the same volume of normal saline. After 24 days of intervention, the tumorigenesis was compared between 2 groups. Results （ 1 ） GSPC-MTDCs had immortalized characteristics. Compared with SU3, the proliferation rate of GSPC-MTDCs was faster and the clone formation rate was significantly higher （38. 1±1.9% vs. 30.2 ±2.7% , P 〈0.01 ）. Transwell chamber invasion test showed that GSPC-MTDCs had stronger invasive ability than SU3 （ 1 042± 49 vs. 782 ± 38, P 〈 0.01 ）. （2） GSPC-MTDCs inoculated into the subcutaneous and caudal veins of non-fluorescent nude mice all formed tumors. At 24 days after 3- BrPA intervention, the tumor masses in the intervention group and the control group were 1.5 ± 0. 6 g and 3.3± 1. 0 g, respectively. The difference was statistically significant （P = 0. 0107 ）. Pathological observation showed that compared with the intervention group, the control group had more abnormal nuclei, more mitosis, abundant blood vessels, obvious

关 键 词：神经胶质瘤 树突状细胞 肿瘤移植 细胞增殖 三溴丙酮酸 肿瘤抑制 小鼠 

分 类 号：R739.4[医药卫生—肿瘤]