Oncotarget

Research Papers:

Overendocytosis of superparamagnetic iron oxide particles increases apoptosis and triggers autophagic cell death in human osteosarcoma cell under a spinning magnetic field

Shaohua Du, Jingxiong Li, Chonghua Du, Zhongming Huang, Guangnan Chen and Weiqi Yan _

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Oncotarget. 2017; 8:9410-9424. https://doi.org/10.18632/oncotarget.14114

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Abstract

Shaohua Du1,*, Jingxiong Li2,*, Chonghua Du3, Zhongming Huang4, Guangnan Chen1, Weiqi Yan1

1Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310008, China

2Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China

3School of Economics, Dongbei University of Finance and Economics, Dalian, 116025, China

4Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital, Hangzhou, 311201, China

*These authors contributed equally to this work

Correspondence to:

Weiqi Yan, email: zeyanweiqi@163.com

Keywords: superparamagnetic iron oxide particles, apoptosis, autophagy, osteosarcoma, spinning magnetic field

Received: April 01, 2016     Accepted: December 12, 2016     Published: December 23, 2016

ABSTRACT

The toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) is still a vital topic of debate and the mechanisms remain unclear. In the present study, overdose SPIONs could induce osteosarcoma cell death and the effects were exaggerated when combined with spinning magnetic field (SMF). In the combination group, mitochondrial transmembrane potential decrease more obviously and reactive oxygen species (ROS) was found to generate much higher in line with that of the apoptosis ratio. Meantime, amount of autophagy was induced. Inhibiting the autophagy generation by 3-methyladenine (3-MA) increase cell viability but decrease the caspase 3/7 and caspase 8 activities in combination groups, and inhibiting apoptosis took the same effect. In the end, the SPIONs effects on xenograft mice was examed by intratumoral injection. The result showed that the combination group could greatly decrease the tumor volume and prolong the lifespan of mice. In sum, the result indicated that overdose SPIONs induced ROS generation, and excessive ROS induced by combination of SPIONs and SMF contribute to autophagy formation, which play a apoptosis-promoting role that formed as a platform to recruits initiate the caspase activities.


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