|Effects of PEI-PEG Nanoparticles Loaded With CD44 siRNA on Inhibition of Growth, Invasion, and Migration of Glioblastoma Cells|
|Parvaneh Mahinfar1, Ahad Mokhtarzadeh2, Behzad Baradaran2, Elham Siasi Torbati3|
|1Department of genetics, North Tehran Branch, Islamic Azad University, Tehran, Iran
2Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran
CJMB 2021; 8: 215-222
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Keywords : Glioblastoma, CD44, siRNA, PEI-PEG
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Objectives: In this study, the inhibitory effects of polyethylene imine glycol (PEI-PEG)/ CD44 siRNA nanostructures on the proliferation, invasion, and apoptosis of U87MG GBM cancer cell line, as well as the expression levels of ALDH1, RANKL, and NOTCH1 were evaluated.
Methods: In this experimental study, PEI-PEG/ CD44 siRNA nanoparticles were synthesized and characterized by atomic force microscopy (AFM), evaluation of size and zeta potential, and Fourier transform infrared (FTIR) spectroscopy. The MTT assay was adopted to evaluate the cytotoxicity of the nanoparticles. The expression levels of target genes were assessed by qRT-PCR. Flow cytometry was used for apoptosis evaluation and Trans well matrigel assay and scratch-migration were employed for investigating the invasion and migration of glioma cells.
Results: The size and zeta potential of PEI-PEG were influenced after CD44 siRNA loading. PEI-PEG loaded with CD44 siRNAs resulted in significant inhibition of glioblastoma cell line in the concentration of 60 pmol (P<0.05). In addition, transfection of glioma cells with CD44 siRNA led to significant downregulation of ALDH1, NOTCH1, and RANKL1 (P<0.05). Transfection of this siRNA also resulted in significant suppression of invasion and migration (P<0.05).
Conclusions: PEI-PEG could effectively form the polyplex in combination with siRNA, be transfected into the U87MG glioma cancer cell line, and inhibit the proliferation, invasion and migration of glioma cells via suppression of ALDH1 and NOTCH1, as well as RANKL1 expression levels.
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