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

Ning Wu, Chunyun Zhang, Changhui Wang, Lairong Song, Weicheng Yao, Aharon Gedanken, Xiukun Lin, Dayong Shi

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish
Pages (from-to)1303-1318
Number of pages16
JournalNanomedicine
Volume13
Issue number11
DOIs
StatePublished - Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 Future Medicine Ltd.

Funding

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.

FundersFunder number
Aoshan Talents Program2015ASTP
NSFC Shandong Provincial Natural Science FoundationZR2014HM004
Chinese Academy of SciencesQYZDB-SSW-DQC014
Qingdao National Laboratory for Marine Science and Technology2015ASKJ02
key research and development project of Shandong province2016GSF115009

    Keywords

    • AKT
    • ERK1/2
    • apoptosis
    • cancer/oncology
    • glioblastoma
    • metal nanoparticles
    • temozolomide resistance
    • therapeutics

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