Effects of Dexmedetomidine on Glioma Cells in the Presence or Absence of Cisplatin

With the extensive use of dexmedetomidine (Dex) in the surgical resection of tumours for its potent sedative and analgesic properties, its effects on various properties of tumours have received increased attention. The study described herein aimed to investigate the effects of Dex on glioma cells in the presence or absence of cisplatin (DDP). Glioma U251 and U87MG cells were treated with different doses (1-50 nM) of Dex for 12 hours, then recultured in a Dex-free medium. In addition, Dex was added to U251 and U87MG cells 12 hours before or simultaneously with a 12-hour DDP treatment. Treatment with Dex increased the viability of both cell lines; this effect continued for at least 24 hours after Dex was removed. A cell invasion assay indicated that Dex inhibited cell invasion at 50 nM, but not at 10 nM. Western blot analysis showed that Dex increased the expression of phosphorylated extracellular-signal-regulated kinase 1/2, phosphoitide 3-kinase and p-AKT, but decreased ROCK protein levels at a dose of 50 nM. Intracellular Ca2+ concentration was decreased by Dex in a dose-dependent manner. DDP toxicity was attenuated by 10 nM Dex added either before or with DDP treatment. However, pretreatment with 50 nM Dex instead enhanced the toxicity of DDP. Single-dose treatment with Dex did not significantly change glioma volume in nude mice, but changed the expression of Ki67 and matrix metalloproteinase-3 in the tumour. In conclusion, this study provides evidence of the regulatory effects of Dex on proliferation, invasion and chemosensitivity of glioma cells, and outlines potential mechanisms for these effects.