Abstract
Cold atmospheric plasma (CAP) is a promising technology against multiple types of cancer. However, the current findings on the effect of CAP on two-dimensional glioblastoma cultures do not consider the role of the tumour microenvironment. The aim of this study was to determine the ability of CAP to reduce and control glioblastoma spheroid tumours in vitro. Three-dimensional glioblastoma spheroid tumours (U87-Red, U251-Red) were consecutively treated directly and indirectly with a CAP using dry He, He + 5% H2O or He + 20% H2O. The cytotoxicity and spheroid shrinkage were monitored using live imaging. The reactive oxygen and nitrogen species produced in phosphate buffered saline (PBS) were measured by electron paramagnetic resonance (EPR) and colourimetry. Cell migration was also assessed. Our results demonstrate that consecutive CAP treatments (He + 20% H2O) substantially shrank U87-Red spheroids and to a lesser degree, U251-Red spheroids. The cytotoxic effect was due to the short- and long-lived species delivered by CAP: they inhibited spheroid growth, reduced cell migration and decreased proliferation in CAP-treated spheroids. Direct treatments were more effective than indirect treatments, suggesting the importance of CAP-generated, short-lived species for the growth inhibition and cell cytotoxicity of solid glioblastoma tumours. We concluded that CAP treatment can effectively reduce glioblastoma tumour size and restrict cell migration, thus demonstrating the potential of CAP therapies for glioblastoma.
Highlights
Glioblastoma multiforme (GBM) is a highly aggressive neoplasia and the most common aggressive tumour on the central nervous system in the adult population [1]
The spheroid core was monitored to determine variations in its area relating to growth inhibition or spheroid shrinkage upon Cold atmospheric plasma (CAP) treatment
We acknowledge the participation of the long-lived species present in Plasma-Treated PBS (pPBS) and in the RONS mix, our results indicate that the short-lived species delivered by plasma during the 2× direct treatment are required to fully inhibit spheroid growth in U87-Red and to delay it in U251-Red
Summary
Glioblastoma multiforme (GBM) is a highly aggressive neoplasia and the most common aggressive tumour on the central nervous system in the adult population [1]. Current therapies against GBM include maximal surgical resection, radiation and chemotherapy. Tumour recurrence is highly common, which contributes to the poor survival rates after diagnosis 15 months; five-year survival of less than 5%) [2,3]. Despite significant improvements in cancer treatment, GBM remains an incurable neoplasia. Cold atmospheric plasmas (CAPs) are currently being explored due to their anti-cancer properties [4,5]. The chemical components produced by CAPs, identified as the active agents responsible for the biological effects, have been extensively studied [6,7]. The reactive oxygen and Cancers 2018, 10, 394; doi:10.3390/cancers10110394 www.mdpi.com/journal/cancers
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