title: Fentanyl inhibits proliferation and invasion of colorectal cancer via β-catenin.
abstract: OBJECTIVE
  Fentanyl is widely used for relieving pain and narcotizing in cancer patients. However, there are few published reports regarding the effects of fentanyl on tumor control and treatment. Here we investigated the effects of fentanyl on tumor growth and cell invasion in the human colorectal carcinoma (HCT116) cells.
  
  
  METHODS
  Nude mice xenografts of HCT116 cells were established to assess the inhibition effect on tumor growth by fentanyl. MTT and Transwell were employed to determine the cell survival rate and cell invasion, respectively. MicroRNAs and mRNAs expression were quantified by real-time PCR. β-catenin and matrix metalloproteinases (MMP-2 and MMP-9) expression were assayed by western blotting. β-Catenin-specific small interfering RNA (Si-β-catenin) and miR-182 mimics were transfected in cells to investigate the mechanism underlying the effects of fentanyl on the colorectal tumor and HCT116 cells.
  
  
  RESULTS
  Treatment with fentanyl inhibited the tumor growth and HCT116 cells invasion. Fentanyl also downregulated the expression of β-catenin and miR-182 in both xenograft tumors and HCT116 cells, and decreased the protein level of MMP-9 in HCT116 cells. Downregulation of β-Catenin resulted in the decrease of miR-182 expression in colorectal cells. In addition, the overexpression of miR-182 reversed the effect of fentanyl on MMP-9 expression and cell invasion of HCT116 cells.
  
  
  CONCLUSIONS
  The current study demonstrated that the inhibition of tumor growth and cell invasion in colorectal cancer by fentanyl is probably due to downregulation of miR-182 and MMP-9 expression by β-catenin.
authors.affiliation: Department of Anesthesiology and Surgery, Department of International Health Care Center, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, Zhejiang, China.
authors.forename: Xiu-Lai
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Surgery, Department of International Health Care Center, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, Zhejiang, China.
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology and Surgery, Department of International Health Care Center, Second Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310009, Zhejiang, China.
authors.forename: Sheng-Li
authors.initials: SL
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005283:Fentanyl / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D035683:MicroRNAs; C540524:Mirn182 microRNA, mouse; D051176:beta Catenin; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D005283:Fentanyl
keywords: Colorectal cancer; HCT116 cells; fentanyl; miR-182; β-catenin