Abstract
Hypoxia has been shown to be a key factor inhibiting the successful treatment of solid tumours. Existing strategies for reducing hypoxia, however, have shown limited efficacy and/or adverse side effects. The aim of this study was to investigate the potential for reducing tumour hypoxia using an orally delivered suspension of surfactant-stabilised oxygen nanobubbles. Experiments were carried out in a mouse xenograft tumour model for human pancreatic cancer (BxPc-3 cells in male SCID mice). A single dose of 100 μL of oxygen saturated water, oxygen nanobubbles or argon nanobubbles was administered via gavage. Animals were sacrificed 30 minutes post-treatment (3 per group) and expression of hypoxia-inducible-factor-1α (HIF1α) protein measured by real time quantitative polymerase chain reaction and Western blot analysis of the excised tumour tissue. Neither the oxygen saturated water nor argon nanobubbles produced a statistically significant change in HIF1α expression at the transcriptional level. In contrast, a reduction of 75% and 25% in the transcriptional and translational expression of HIF1α respectively (p<0.001) was found for the animals receiving the oxygen nanobubbles. This magnitude of reduction has been shown in previous studies to be commensurate with an improvement in outcome with both radiation and drug-based treatments. In addition, there was a significant reduction in the expression of vascular endothelial growth factor (VEGF) in this group and corresponding increase in the expression of arrest-defective protein 1 homolog A (ARD1A).
Highlights
Hypoxia, i.e. a reduction in dissolved oxygen concentration below physiologically normal levels, has been identified as playing a critical role in the progression of several diseases, including many types of cancer [1]
I.e. a reduction in dissolved oxygen concentration below physiologically normal levels, has been identified as playing a critical role in the progression of several diseases, including many types of cancer [1]. It arises as a consequence of the rapid proliferation and atypical vasculature of cancerous tissue
The aim of this study was to assess the potential of a further alternative method for reducing tumour hypoxia using an orally delivered suspension of sub-micrometre sized oxygen nanobubbles stabilised by a surfactant
Summary
I.e. a reduction in dissolved oxygen concentration below physiologically normal levels, has been identified as playing a critical role in the progression of several diseases, including many types of cancer [1]. In solid tumours, it arises as a consequence of the rapid proliferation and atypical vasculature of cancerous tissue. It arises as a consequence of the rapid proliferation and atypical vasculature of cancerous tissue This results in the development of areas in which oxygen demand outstrips supply [2]. PLOS ONE | DOI:10.1371/journal.pone.0168088 December 30, 2016
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