Fentanyl inhibits cell invasion and migration by modulating NF-κB activation in glioma.

ABSTRACT

Fentanyl is widely used for anesthesia and analgesia in cancer patients. Recent studies have revealed its anti-growth effect in several categories of cancer. Gliomas are the most common primary tumors in the central nervous system with poor prognosis. To investigate the effects of fentanyl on gliomas, glioma cells were treated with different concentrations of fentanyl both in vitro and in vivo. Consequences of proliferation and invasive phenotypes, and related protein expression were evaluated in two human glioma cell lines (U251 and U87). Naloxone, Mu Opioid Receptor (MOR) antagonist, was introduced into culture media to assess the involvement of MOR in Fentanyl-mediated changes. When compared with control group, it could be found that Fentanyl inhibited function of glioma cells only at high concentrations. Western blot and immunofluorescence results revealed that Fentanyl exerted its action via modulating NF-κB (P65) activation which is likely independent of MOR. Moreover, overexpression of P65 by transfection P65-expressing vector restored the invasion and migration of glioma cells, which were inhibited by Fentanyl. In summary, this study showed that opioid pain medication Fentanyl was capable of decreasing invasiveness of glioma cells at a high concentration both in vitro and in vivo, likely via modulating P65 activation.