Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets

Teng Zhou, Bo Zhang, Peng Wei, Yipeng Du, Hejiang Zhou, Meifang Yu, Liang Yan, Wendi Zhang, Guangjun Nie, Chunying Chen, Yaping Tu, Taotao Wei

Research output: Contribution to journalArticle

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Abstract

Recent advances in nanomedicine provide promising alternatives for cancer treatment that may improve the survival of patients with metastatic disease. The goal of the present study was to evaluate graphene oxide (GO) as a potential anti-metastatic agent. For this purpose, GO was modified with polyethylene glycol (PEG) to form PEG-modified GO (PEG-GO), which improves its aqueous stability and biocompatibility. We show here that PEG-GO exhibited no apparent effects on the viability of breast cancer cells (MDA-MB-231, MDA-MB-436, and SK-BR-3) or non-cancerous cells (MCF-10A), but inhibited cancer cell migration invitro and invivo. Analysis of cellular energy metabolism revealed that PEG-GO significantly impaired mitochondrial oxidative phosphorylation (OXPHOS) in breast cancer cells; however, PEG-GO showed no effect on OXPHOS in non-cancerous cells. To explore the underlying mechanisms, a SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to quantify protein expression in PEG-GO-exposed breast cancer versus non-cancerous cells. The results indicated that PEG-GO selectively down-regulated PGC-1α in breast cancer cells and thus modified the expression of diverse energy generation-related proteins, which accounts for the inhibition of OXPHOS. The inhibition of OXPHOS by PEG-GO significantly reduced ATP production and impaired assembly of the F-actin cytoskeleton in breast cancer cells, which is required for the migratory and invasive phenotype of cancer cells. Taken together, these effects of PEG-GO on cancer cell metastasis may allow the development of a new approach to treat metastatic breast cancer.

Original languageEnglish
Pages (from-to)9833-9843
Number of pages11
JournalBiomaterials
Volume35
Issue number37
DOIs
StatePublished - Dec 1 2014

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Graphite
Nanosheets
Oxides
Graphene
Energy Metabolism
Polyethylene glycols
Cells
Breast Neoplasms
Neoplasm Metastasis
Oxidative Phosphorylation
Labeling
Neoplasms
Nanomedicine
Isotope Labeling
Proteins
Medical nanotechnology
Enzyme inhibition
Oncology
Adenosinetriphosphate
Actin Cytoskeleton

All Science Journal Classification (ASJC) codes

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics
  • Medicine(all)

Cite this

Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets. / Zhou, Teng; Zhang, Bo; Wei, Peng; Du, Yipeng; Zhou, Hejiang; Yu, Meifang; Yan, Liang; Zhang, Wendi; Nie, Guangjun; Chen, Chunying; Tu, Yaping; Wei, Taotao.

In: Biomaterials, Vol. 35, No. 37, 01.12.2014, p. 9833-9843.

Research output: Contribution to journalArticle

Zhou, Teng ; Zhang, Bo ; Wei, Peng ; Du, Yipeng ; Zhou, Hejiang ; Yu, Meifang ; Yan, Liang ; Zhang, Wendi ; Nie, Guangjun ; Chen, Chunying ; Tu, Yaping ; Wei, Taotao. / Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets. In: Biomaterials. 2014 ; Vol. 35, No. 37. pp. 9833-9843.
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