Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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).

Original publication

DOI

10.1371/journal.pone.0168088

Type

Journal article

Journal

PloS one

Publication Date

01/2016

Volume

11

Addresses

Oxford Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom.

Keywords

Cell Line, Tumor, Animals, Humans, Mice, Mice, SCID, Pancreatic Neoplasms, Disease Models, Animal, Neovascularization, Pathologic, Oxygen, Angiogenesis Inhibitors, Vascular Endothelial Growth Factor A, Administration, Oral, Xenograft Model Antitumor Assays, Signal Transduction, Gene Expression Regulation, Neoplastic, Nanostructures, Male, Hypoxia-Inducible Factor 1, alpha Subunit, Nanoparticles, Tumor Hypoxia