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The Effects and Molecular Mechanisms of MiR-106a in Multidrug Resistance Reversal in Human Glioma U87/DDP and U251/G Cell Lines

机译:MiR-106a在人胶质瘤U87 / DDP和U251 / G细胞株多药耐药逆转中的作用及其分子机制

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摘要

Chemotherapy resistance is one of the major obstacles to effective glioma therapy. Currently, the mechanism underlying chemotherapy resistance is unclear. A recent study showed that miR-106a is an important molecule involved in chemotherapy resistance. To explore the effects and mechanisms of miR-106a on multidrug resistance reversal in human glioma cells, we silenced miR-106a expression in the cisplatin-resistant U87 (U87/DDP) and the gefitinib-resistant U251 (U251/G) glioma cell lines and measured the resulting drug sensitivity, cell apoptosis rate and rhodamine 123 content. In addition, we detected decreased expression of P-glycoprotein, MDR1, MRP1, GST-π, CDX2, ERCC1, RhoE, Bcl-2, Survivin and Topo-II, as well as reduced production of IL-6, IL-8 and TGF-β in these cell lines. Furthermore, we found decreased expression of p-AKT and transcriptional activation of NF-κB, Twist, AP-1 and Snail in these cell lines. These results suggest that miR-106a is a promising therapeutic target for the treatment of human multidrug resistant glioma.
机译:耐药性是有效的神经胶质瘤治疗的主要障碍之一。目前,尚不清楚化疗耐药的潜在机制。最近的一项研究表明,miR-106a是参与化疗耐药性的重要分子。为了探索miR-106a对人胶质瘤细胞多药耐药逆转的作用和机制,我们沉默了耐顺铂U87(U87 / DDP)和耐吉非替尼U251(U251 / G)胶质瘤细胞系中miR-106a的表达。并测量所得药物敏感性,细胞凋亡率和若丹明123含量。此外,我们检测到P糖蛋白,MDR1,MRP1,GST-π,CDX2,ERCC1,RhoE,Bcl-2,Survivin和Topo-II的表达降低,以及IL-6,IL-8和这些细胞系中的TGF-β。此外,我们发现在这些细胞系中,p-AKT的表达减少,NF-κB,Twist,AP-1和Snail的转录激活。这些结果表明,miR-106a是用于治疗人多药耐药性神经胶质瘤的有希望的治疗靶标。

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