Research Article

Zinc-doped copper oxide nanocomposites reverse temozolomide resistance in glioblastoma by inhibiting AKT and ERK1/2

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China

Laboratory for Marine Drugs & Bioproducts, Qingdao National Laboratory for Marine Science & Technology, Qingdao, China

Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China

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Chunyun Zhang

Department of Neurosurgery, Qilu Hospital of Shandong University, Qingdao, China

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Changhui Wang

Shanghai Neuromedical Center, Qingdao University, Shanghai, China

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Lairong Song

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

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Weicheng Yao

Department of Neurosurgery, Qingdao University, Qingdao, China

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Aharon Gedanken

Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel

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Xiukun Lin

**Co-author for correspondence:

E-mail Address: xiukunlin@126.com

Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China

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Dayong Shi

*Author for correspondence:

E-mail Address: shidayong@qdio.ac.cn

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China

Laboratory for Marine Drugs & Bioproducts, Qingdao National Laboratory for Marine Science & Technology, Qingdao, China

Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, China

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Published Online:27 Jun 2018https://doi.org/10.2217/nnm-2017-0359

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Abstract

Aim: To assess the effect of zinc-doped copper oxide nanocomposites (nZn-CuO NPs) on glioblastoma therapy.Materials & methods: nZn-CuO NPs were synthesized by sonochemical method and its antitumor effects and underlying molecular mechanisms were investigated both in vitro and in vivo. Results: After nZn-CuO NPs treatment, cell proliferation was significantly inhibited in dividing cancer cells but less toxicity was observed in normal cells. In vivo studies show that nZn-CuO NPs inhibited tumor growth in a dose-dependent manner. Further study found that nZn-CuO NPs trigger cell reactive oxygen species (ROS) generation and intrinsic apoptotic pathway. In temozolomide resistance glioblastoma, nZn-CuO NPs disturb cell growth and sphere formation by inhibiting AKT and ERK1/2 activation. Conclusion: nZn-CuO NPs possess the potential to be developed as a novel anti-tumor agent, especially to treat temozolomide resistance glioblastoma.

Keywords:

References

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Vol. 13, No. 11

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History

Received 29 November 2017

Accepted 27 February 2018

Published online 27 June 2018

Published in print June 2018

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Financial & competing interest disclosure

This work was supported by the key research and development project of Shandong province (2016GSF115009) and key research program of Frontier Sciences, CAS (QYZDB-SSW-DQC014) and partly supported by NSFC Shandong Provincial Natural Science Foundation (grant number ZR2014HM004) and Qingdao National Laboratory for Marine Science and Technology (number 2015ASKJ02), and Aoshan Talents Program Supported by Qingdao National Laboratory for Marine Science and Technology (number 2015ASTP). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal experiments were performed according to guidelines determined by Institute of Oceanology, Chinese Academy of Sciences committees for animal welfare and use of human subjects.

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