Fentanyl Increases Colorectal Carcinoma Cell Apoptosis by Inhibition of NF-κB in a Sirt1-dependent Manner


Background: Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recentlyit has become considered to also act as an antitumor agent. The study present was designed to investigate theeffects of fentanyl on colorectal cancer cell growth and plausible mechanisms. Materials and
Methods: The humancolorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 wastested by MTT assay, and apoptosis by flow cytometry and caspase-3 activity. The expression of Sirt1 and NF-κB were evaluated by Western blotting and the levels of Sirt1 and NF-κB by fluorescence method. SiRNA wasused to silence and Ad-Sirt1 to overexpress Sirt1.
Results: Our data showed that fentanyl could inhibit tumorgrowth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with controlcells without treatment, HCT116 cells that were incubated with fentanyl had a higher apoptotic rate. Moreover,fentanyl could increase expression and activity of Sirt1 and inhibitor expression and activity of NF-κB, whichmight be mechanisms of fentanyl action.
Conclusions: Fentanyl increased colorectal carcinoma cell apoptosisby inhibition of NF-κB activation in a Sirt1-dependent manner.