Wang Qin, Wang Zhenlian, Chu LinYang, Li Xu, Kan Pengcheng, Xin Xin, Zhu Yu, Yang Ping
Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin 300060, China.
Department of Nursing, School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou 325003, China.
PLoS One. 2015 May 7;10(5):e0125473. doi: 10.1371/journal.pone.0125473. eCollection 2015.
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.
化疗耐药是有效治疗胶质瘤的主要障碍之一。目前,化疗耐药的潜在机制尚不清楚。最近的一项研究表明,miR-106a是参与化疗耐药的重要分子。为了探讨miR-106a对人胶质瘤细胞多药耐药逆转的影响及机制,我们在顺铂耐药的U87(U87/DDP)和吉非替尼耐药的U251(U251/G)胶质瘤细胞系中沉默miR-106a的表达,并检测由此产生的药物敏感性、细胞凋亡率和罗丹明123含量。此外,我们检测到这些细胞系中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TGF-β的产生减少。此外,我们发现这些细胞系中p-AKT的表达降低,NF-κB、Twist、AP-1和Snail的转录激活减少。这些结果表明,miR-106a是治疗人多药耐药胶质瘤的一个有前景的治疗靶点。