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Inhibition of human glioblastoma cell invasion involves PION@E6 mediated autophagy process

Authors Ren Z, Liang J, Zhang P, Chen J, Wen J

Received 2 January 2019

Accepted for publication 13 February 2019

Published 29 March 2019 Volume 2019:11 Pages 2643—2652

DOI https://doi.org/10.2147/CMAR.S200151

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Zhongyu Ren, Jing Liang, Peng Zhang, Jianjiao Chen, Jian Wen

Affiliated Hospital of Guilin Medical University, Guilin Medical University, Guangxi, People’s Republic of China

Background: Glioblastoma (GBM) is the most severe brain cancer due to its ability to invade surrounding brain tissue. Iron oxide nanoparticles (ION) could effectively induce a decrease of cell migration/invasion. Also IONs could generate ROS stress which induces autophagy elevation. Autophagy is associated with both anti-tumorigenesis and protumorigenesis.
Objective: To explore the effect of PEGylated IONs (PION@E6) on the GBM cell invasion and its mechanism based on autophagy.
Materials and methods: PION@E6 were prepared and characterized according to our previous study. After incubation of U251 cells with PION@E6, cellular uptake of PION@E6 and cell viability were tested by Prussian blue staining and Cell Counting Kit-8, respectively. The migration and invasive capability was assessed by transwell cell migration and invasion assay. Expressions of autophagy biomarkers were detected by Western blotting. Intracellular ROS level was determined using 2′–7′-dichlorodihydrofluorescein diacetate.
Results: Average hydrate particle size and zeta potential of PION@E6 were 37.86±12.90 nm and –23.8 mV, respectively, and uniformly distributed nanoparticles with an average diameter of 10 nm were observed by TEM. Chlorin e6 successfully incorporated onto PION@E6 was demonstrated by ultraviolet and visible absorption spectrophotometry, and PION@E6 owning excellent water solubility and stability were showed by Colloid stability test. PION@E6 were successfully taken up by U251 cells with Prussian blue staining, and they showed in vitro cytotoxicity to glioma cells after long incubation of 72 hours. Migration/invasion of cells was significantly inhibited by PION@E6, which could be counteracted by pretreatment with 3-MA. Additionally, the expression of beclin-1, IC3I, and IC3II proteins was higher, whereas that of p62 protein was lower. Moreover, a dose dependent intracellular ROS generation of PION@E6 was detected.
Conclusion: Invasiveness of human GBM cells involves the PION@E6-mediated autophagy process, which may be related to the intracellular ROS induced by PION@E6.

Keywords: iron oxide nanoparticle, glioblastoma, invasiveness, autophagy


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