Abstract
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.
Highlights
Platinum drugs and epidermal growth factor receptor (EGFR) inhibitors are the potential selectable anticancer drugs for the clinical treatment of low grade glioma patient and children patient in China [1,2]
MiR-106a reduces the sensitivity of tumor cells to cisplatin and gefitinib
To explore the role of miR-106a in tumor cell drug resistance, we detected the expression of miR-106a in normal U87 cells and the cisplatin-resistant cell line U87/DDP, as well as in normal and gefitinib-resistant U251 cells (U251/G, see Materials and Methodology for construction method)
Summary
Platinum drugs and epidermal growth factor receptor (EGFR) inhibitors are the potential selectable anticancer drugs for the clinical treatment of low grade glioma patient and children patient in China [1,2]. Tumor cells resist the cytotoxic effects of cisplatin through a variety of mechanisms, such as increasing drug efflux, PLOS ONE | DOI:10.1371/journal.pone.0125473. Previous studies have found that the mechanisms by which tumor cells develop drug resistance include reduced drug absorption, increased drug efflux through the ABC (ATP-binding cassette) transporter protein, enhanced tumor cell ability to detoxify anticancer drugs through the reductase system, reduced tumor apoptosis rate through regulating the apoptosis pathway, and modulation of cytokine production to alter the tumor microenvironment and signaling pathways [7]
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