Abstract

Resistance to chemotherapy and the side effects of anticancer drugs are the major obstacles for glioma treatment. The aim of the present study was to develop a novel approach for the treatment of gliomas that improved the therapeutic effect; the anticancer drug, doxorubicin (DOX), was combined with short interfering (si)RNA and monomethoxy polyethylene glycol polyethylenimine superparamagnetic iron oxide nanoparticle (mPEG-PEI-SPION), a magnetic resonance imaging (MRI)-visible nanoparticle. Specific siRNA molecules, delivered by mPEG-PEI-SPION, were employed to knockdown the PIN2-interacting protein 1 (PinX1) gene in C6 glioma cells. PinX1 is a nucleolar protein associated with telomere and telomerase. C6 cells were treated with DOX and/or PinX1-siRNA. The results of the transfection experiments revealed that siRNA/mPEG-PEI-SPION was transfected into C6 cells with high efficiency. PinX1-siRNA was unable to inhibit C6 cells, while in the PinX1-siRNA + DOX group, the same dose of DOX caused an increased loss of cell viability. Therefore, mPEG-PEI-SPION was shown to be viable for siRNA delivery into C6 cells and coadministration of DOX with PinX1-siRNA may be a potential therapeutic method for inhibiting gliomas.

Highlights

  • Gliomas are the most common primary malignant tumor of the adult central nervous system, accounting for ~40% ofKey words: monomethoxy polyethylene glycol polyethyleneimine superparamagnetic iron oxide nanoparticle, doxorubicin, PIN2‐interacting protein 1, short interfering RNA, glioma intracranial tumors [1]

  • A bicinchoninic acid (BCA) kit was purchased from Pierce Biotechnology, Inc. (Rockford, IL, USA) and a TeloTAGGG Telomerase PCR ELISA kit was purchased from Roche Diagnostics Corporation (Indianapolis, IN, USA)

  • Sizes of PinX1‐siRNA/mPEG‐PEI‐Superparamagnetic iron oxide nanoparticle (SPION) ranged between 100 and 150 nm, which was a suitable size for higher specific surface area and better penetrability

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Summary

Introduction

Gliomas are the most common primary malignant tumor of the adult central nervous system, accounting for ~40% of. The C6 cell line is a rat glioma cell line that is induced by N‐nitrosomethylurea. This cell line is widely adopted for glioma study due to the histocompatibility in various categories of rats and the infiltrative growth pattern that is similar to human glioma [4]. C6 cells were employed in the present study as the cell model for glioma

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