Overendocytosis of superparamagnetic iron oxide particles increases apoptosis and triggers autophagic cell death in human osteosarcoma cell under a spinning magnetic field
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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
Weiqi Yan, email: email@example.com
Keywords: superparamagnetic iron oxide particles, apoptosis, autophagy, osteosarcoma, spinning magnetic field
Received: April 01, 2016 Accepted: December 12, 2016 Published: December 23, 2016
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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