Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT

Nagendra Kumar Kaushik, Neha Kaushik, Ki Chun Yoo, Nizam Uddin, Ju Sung Kim, Su Jae Lee, Eun Ha Choi

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Metastasis, the primary cause of tumor cell transformation, is often activated during cancer invasion and progression and is associated with poor therapeutic outcomes. The effects of combined treatments that included PEG-coated gold nanoparticles (GNP) and cold plasma on epithelial-mesenchymal transition (EMT) and the maintenance of cancer stem cells (CSC) have not been described so far. Here, we report that co-treatment with GNP and cold plasma inhibited proliferation in cancer cells by abolishing the activation of the PI3K/AKT signaling axis. In addition, co-treatment reversed EMT in solid tumor cells by reducing the secretion of a number of proteins, resulting in the upregulation of epithelial markers such as E-cadherin along with down-regulation of N-Cadherin, Slug and Zeb-1. The inhibition of the PI3K/AKT pathway and the reversal of EMT by co-treatment prevented tumor cells growth in solid tumors. Furthermore, we show that GNP and plasma also suppresses tumor growth by decreasing mesenchymal markers in tumor xenograft mice models. Importantly, co-treatment resulted in a substantial decrease in sphere formation and the self-renewal capacity of glioma-like stem cells. Together, these results indicate a direct link between a decrease of EMT and an increase in cell death in solid tumors following co-treatment with cold plasma and GNP.

Original languageEnglish
Pages (from-to)118-130
Number of pages13
JournalBiomaterials
Volume87
DOIs
StatePublished - 2016 May 1

Keywords

  • Cold plasma
  • Epithelial-mesenchymal transition
  • Glioma-like stem cells
  • Gold nanoparticles
  • Solid cancers
  • Stemness

Fingerprint Dive into the research topics of 'Low doses of PEG-coated gold nanoparticles sensitize solid tumors to cold plasma by blocking the PI3K/AKT-driven signaling axis to suppress cellular transformation by inhibiting growth and EMT'. Together they form a unique fingerprint.

  • Cite this