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.
Keywords: Cold plasma; Epithelial–mesenchymal transition; Glioma-like stem cells; Gold nanoparticles; Solid cancers; Stemness.
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