title: Fentanyl increases colorectal carcinoma cell apoptosis by inhibition of NF-κB in a Sirt1-dependent manner.
abstract: BACKGROUND
  Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recently it has become considered to also act as an antitumor agent. The study present was designed to investigate the effects of fentanyl on colorectal cancer cell growth and plausible mechanisms.
  
  
  METHODS
  The human colorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 was tested 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 was used to silence and Ad-Sirt1 to overexpress Sirt1.
  
  
  RESULTS
  Our data showed that fentanyl could inhibit tumor growth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with control cells 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, which might be mechanisms of fentanyl action.
  
  
  CONCLUSIONS
  Fentanyl increased colorectal carcinoma cell apoptosis by inhibition of NF-κB activation in a Sirt1-dependent manner.
authors.affiliation: The Department of Anesthesiology and Surgery, International Healthcare Center, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China E-mail : sheli_zhou0811@163.com.
authors.forename: Xiu-Lai
authors.initials: XL
authors.lastname: Zhang
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Chen
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005283:Fentanyl / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D009294:Narcotics / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D016328:NF-kappa B; D009294:Narcotics; D034741:RNA, Small Interfering; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005283:Fentanyl