Synergistic inhibition of human glioma cell line by temozolomide and PAMAM-mediated miR-21i
Synergistic inhibition of human glioma cell line by temozolomide and PAMAM-mediated miR-21i
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DOI：
10.1002/app.37823
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发表时间：
2013-01
影响因子：
3
通讯作者：
Xiaomin Qian;Zhen-dong Shi;Yu Ren;Chaoyong Liu;Yanbin Ji;Li-xia Long;P. Pu;J. Sheng;Xubo Yuan-Xubo
中科院分区：
文献类型：
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作者：
Xiaomin Qian;Zhen-dong Shi;Yu Ren;Chaoyong Liu;Yanbin Ji;Li-xia Long;P. Pu;J. Sheng;Xubo Yuan-Xubo
替莫唑胺（TMZ）是一种很有前途的治疗胶质母细胞瘤的化疗药物。然而，耐药性发展迅速，频率很高。因此，迫切需要努力克服耐药性。本研究以聚酰胺-胺（PAMAM）树枝状大分子为载体，将microRNA-21抑制剂（miR-21 i）导入U87细胞，观察miR-21 i与TMZ联合应用对胶质瘤化疗的敏感性。流式细胞术分析显示了与PAMAM复合后microRNA-21抑制剂的摄取效率。实时荧光定量PCR和原位杂交结果显示，与TMZ或miR-21 i处理的细胞相比，miR-21 i和TMZ同时处理的细胞microRNA-21（miR-21）水平显著降低。miR-21 i转染后，TMZ对胶质瘤细胞的IC 50值显著降低，从而增强了化疗敏感性。下调miR-21表达可促进细胞凋亡，同时抑制细胞侵袭。总之，TMZ和miR-21 i联合处理胶质瘤细胞可产生抑制人胶质瘤细胞系的协同效应。© 2012 Wiley Periodicals，Inc. J.应用聚合物科学，2013
Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly and with a high frequency. Efforts to overcome chemoresistance are, therefore, critically needed. In present study, a poly(amidoamine; PAMAM) dendrimer was used as a vector to deliver microRNA-21 inhibitor (miR-21i) into U87 cells and the chemosensitivity of the combination effect of miR-21i and TMZ for glioma therapy was investigated. Flow cytometry analysis showed the uptake efficiency of microRNA-21 inhibitor after complexation with PAMAM. Real-time PCR and in situ hybridization indicated that, compared with TMZ or miR-21i treated cells, cells simultaneously treated with miR-21i and TMZ showed a remarkable decrease in the microRNA-21 (miR-21) level. The transfection of miR-21i enhanced the chemosensitivity by significantly decreasing the IC50 value of TMZ to glioma cells. Knockdown of miR-21 promoted the cells' apoptosis, and at the same time, inhibited cell invasion. In conclusion, the combination treatment of glioma cells with TMZ and miR-21i could yield a synergistic effect in inhibition of human glioma cell line. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013