Background: Growing evidences indicate that inhalational anaesthetics can enhance the growth and malignant potential of tumour cells and may affect tumour recurrence after surgery. Tumour stem cells play a vital role in tumour recurrence. This study investigates the effect of sevoflurane on glioma stem cells (GSCs) in vitro and the underlying molecular mechanisms in this process.
Methods: Cultured GSCs were exposed to clinically relevant concentrations and durations of sevoflurane exposure. Cell proliferation and self-renewal capacity were determined. Expression of the stem cell marker CD133, vascular endothelial growth factor (VEGF), hypoxia-inducible factors (HIFs), and phosphorylated Akt, which is a protein kinase invoved in multiple cellular processes, were measured using western blotting. Small interfering RNAs and an Akt inhibitor were used to investigate specific pathways.
Results: Compared with controls, cells exposed to 2% sevoflurane for 6 h induced a larger number of proliferated cells (31.2±7.6% vs 19.0±5.8%; P<0.01). Levels of CD133, VEGF, HIF-1α, HIF-2α, and p-Akt were up-regulated by sevoflurane in a time- and concentration-dependent manner. Small interfering RNA against HIFs decreased the percentage of proliferating GSCs after sevoflurane exposure and pre-treatment of cells with an Akt inhibitor abrogated the expression of HIFs induced by sevoflurane.
Conclusions: Sevoflurane can promote the expansion of human GSCs through HIFs in vitro. Inhaled anaesthetics may enhance tumour growth through tumour stem cells.
Keywords: AC133 antigen; glioma; hypoxia-inducible factor-1α; neoplastic stem cells; sevoflurane.
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