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反义miR-21抑制异种移植U87人脑胶质瘤生长的体内研究
引用本文:周旋,康春生,浦佩玉,尤永平,许鹏,张安玲,王广秀,贾志凡,刘晓智,徐嵩,傅震,赵鹏. 反义miR-21抑制异种移植U87人脑胶质瘤生长的体内研究[J]. 中华神经医学杂志, 2008, 7(9)
作者姓名:周旋  康春生  浦佩玉  尤永平  许鹏  张安玲  王广秀  贾志凡  刘晓智  徐嵩  傅震  赵鹏
作者单位:1. 天津医科大学总医院神外科,天津,300052
2. 天津市神经病学研究所神经肿瘤研究室,天津,300052
3. 南京医科大学第一附属医院神经外科,南京,210029
基金项目:国家自然科学基金,教育部跨世纪优秀人才培养计划 
摘    要:目的 探讨敲低miR-21表达抑制裸鼠皮下荷U87人脑胶质瘤生长的疗效和机制.方法 原位注射miR-21反义寡聚核苷酸(AS-miR-21)治疗裸鼠皮下荷U87人脑胶质瘤.定时测量肿瘤大小评估原位注射AS-miR-21的治疗效果.使用RT-PCR和原位杂交方法 鉴定治疗后miR-21表达水平,采用HE染色和免疫组织化学染色(增殖细胞核抗原、细胞周期抑制因子-21、基质金属蛋白酶-9和隔蛋白-7)评价治疗后肿瘤生物学性状的变化,TUNEL法检测肿瘤细胞凋亡. 结果 肿瘤生长曲线显示AS-miR-21治疗组肿瘤生长速度及体积明显小于对照组与无义序列治疗组,差异有统计学意义(F=6.056,P=0.007);RT-PCR检测显示AS-miR-21治疗组miR-21表达下调为对照组的(0.031±0.008)%;原位杂交显示AS-miR-21治疗组miR-21表达水平较对照组与无义序列治疗组下调:组织病理学检测表明AS-miR-21治疗后肿瘤恶性度降低;TUNEL法检测可见AS-miR-21治疗组细胞凋亡数明显高于对照组与无义序列治疗组,差异有统计学意义(F=141.021,P=0.000). 结论 以miR-21作为靶点治疗异种移植U87人脑胶质瘤效果令人满意,miR-21可作为人脑胶质瘤基因治疗的侯选靶点.

关 键 词:反义寡聚核苷酸  神经胶质瘤  基因治疗

Suppressive effect of knockdown of miR-21 expression on U87 human glionto growth in vivo
ZHOU Xuan,KANG Chun-sheng,PU Pei-yu,YOU Yong-ping,XU Peng,ZHANG An-ling,WANG Guang-xiu,JIA Zhi-fan,LIU Xiao-zhi,XU Song,FU Zhen,ZHAO Peng. Suppressive effect of knockdown of miR-21 expression on U87 human glionto growth in vivo[J]. Chinese Journal of Neuromedicine, 2008, 7(9)
Authors:ZHOU Xuan  KANG Chun-sheng  PU Pei-yu  YOU Yong-ping  XU Peng  ZHANG An-ling  WANG Guang-xiu  JIA Zhi-fan  LIU Xiao-zhi  XU Song  FU Zhen  ZHAO Peng
Abstract:Objective To study the suppressive effect of knockdown of miR-21 on the U87 human giioma xenograft growth and the possible mechanism. Methods Nude mice bearing U87 human glioblastoma subcutaneously were treated with miRNA-21 anfisense oligonucleotides(AS-miR-21)intratumomlly every 3 d until the observation peded ended.The tumor volume of the mice treated withAS-miR-21 was measured regularly as compared with that in the control untreated mice and in the mice treated with scramble oligonucelotides(ODN).Finally,the tumors were removed from nude mice for the examination.In-sire hybridization and real-time PCR were conducted to detect the miRNA expression of miR-21.The biological charaetedsties of the tumors were evaluated by HE and immunohistochemieal staining, and the cell apoptosis was detected by TUNEL method. Resulls During the observation period,the tumor growth was delayed and the final tumor volume of AS-miR-21 heated group was smaller than that in the control and scramble ODN treatedg roup(F=6-056,P=0.007).The expression of miRNA precursor was knocked down in As-miRNA treated tunlors compared with that in untreated or scramble ODN treated tumors.Histopathological examination exhibited the appearance of degraded malignancy.The expressions of PCNA and MMP-9 were down-regulated while Septin-7 and P21 were up-regulated and apoptotic index was increased significantly (F=141.021,P=000) as well.Conclusion The suppressive effect of anti-miR-21 ODNs on the growth of U87 human glioma xenogratts is significant and miR-21 Call be taken as a candidate for gene therapy ofhuman glioma.
Keywords:miR-21
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