反义miR-19a／b抑制LN229人脑胶质瘤生长的体内实验研究  

Inhibitory effect of knocking down micro19a/b on LN229 human gfioma cell growth in vivo

作　　者：孙即奎[1] 浦佩玉[1] 张安玲[1] 王广秀[1] 杨卫东[1] 贾志凡[1] 

机构地区：[1]天津医科大学总医院神经病学研究所神经肿瘤室,300052

出　　处：《中华神经外科杂志》2013年第11期1110-1113,共4页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金资助项目（30872985,81101915）

摘　　要：目的探讨敲低miR-19a／b表达抑制裸鼠荷人脑胶质瘤细胞LN229移植瘤生长的疗效和机制。方法原位注射miR-19a／b反义寡聚核苷酸（AS—miR-19a／b）治疗裸鼠皮下荷LN229人脑胶质瘤模型。Real—time PCR方法鉴定治疗后miR-19a／b表达水平，采用HE染色和免疫组织化学染色检测评价治疗后肿瘤增殖、凋亡等生物学性状及核心信号通路成员相关指标的变化，包括PTEN、AKT、P—AKT等；TUNEL法检测肿瘤细胞凋亡。结果AS—miR-19a／b治疗组肿瘤生长速度及体积明显小于对照组与无义序列组，差异有统计学意义（F=19．221，P〈0．05）；其miR-19a／b表达下调为对照组的0．187±0．025；组织病理学检测表明AS—miR-19a／b治疗后肿瘤恶性表型有所逆转。结论以miR-19a／b作为靶点治疗异种移植LN229人脑胶质瘤效果显著，miR-19a／b可作为人脑胶质瘤靶向治疗的侯选靶点。Objective To study the suppressive effect of knocking down miR - 19a/b on the LN229 human glioma xenograft growth and the possible mechanism. Methods Nude mice bearing subcutaneous LN229 human glioblastoma were established and treated with miR19a/b antisense olignueleotides（ AS -miR - 19a/b） intraumorally every other day until the obselvation period ended. The tumor volume of the mice treated with AS - miR - 19a/b was measured regularly as compared with that in the control untreated mice and in the mice treated with scramble oligonucelotides（ scr- ODN）. Finally, the tumors were removed from nude mice for the examination. Real - time PCR was conducted to detect the expression of miR19a/b. The histopathological characteristics and the members of core signaling pathway - PTEN/AKT in gliomas were evaluated by HE and immunohistochemieal staining, respectively, and the cell apoptosis was deteetd by TUNEL method. Results In AS - miRNA treated group, the tumor growth was delayed and the final tumor volume was smaller than that in the control and scr - ODN treated group（ F = 19. 221, P 〈0.05） ,and the expression of miRNA19a/b was knocked down. Histopathological examination exhibited somewhat reversal of malignant phenotype of tumors, apoptotie index was increased significantly as well. Conclusions Anti -miR19a/b suppressed the growth of LN229 human gliomas xenografts significantly. MiR19a/b could be a candidate for targeted therapy of human glioma.

关 键 词：神经胶质瘤移植 miR-19a b反义寡核苷酸 靶向治疗 

分 类 号：R739.4[医药卫生—肿瘤]