title: Tramadol inhibits proliferation, migration and invasion via α2-adrenoceptor signaling in breast cancer cells.
abstract: OBJECTIVE
  The aim of this study was to examine the function of tramadol on cell proliferation, migration and invasion in breast cancer cells in vitro, and to evaluate the effect of tramadol in vivo. Further, we explore the mechanism accounting for the role of tramadol on breast cancer cells.
  
  
  METHODS
  Cell proliferation was detected by the methyl thiazolyl tetrazolium (MTT) assay. Wound healing assay and transwell assay was applied to quantify the migration and invasion ability of MDA-MB-231 cells. The expression of endogenous α2-adrenoceptor and ERK was measured by Western blotting.
  
  
  RESULTS
  Tramadol at a clinical dose of up to 2 μM significantly inhibited the proliferation, migration and invasion in a time-dependent manner from day 0 to 28 in vitro. Moreover, tramadol suppressed the growth of xenotransplant tumor in vivo markedly. Furthermore, the protein levels of α2-adrenoceptor and phosphorylated ERK were decreased by tramadol, whereas the expression of total ERK remained unchanged. In addition, downregulation of α2-adrenoceptor by yohimbine could mimic the effect of tramadol treatment.
  
  
  CONCLUSIONS
  Collectively, we demonstrated that tramadol could inhibit proliferation, migration and invasion of breast cancers via inactivating α2-adrenoceptor signaling pathway. Our data provide the experimental fundamental for further investigation of the anti-cancer effect of tramadol in breast cancer cells.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China. shaohuawang_nj@sina.com.
authors.forename: M
authors.initials: M
authors.lastname: Xia
authors.forename: J-H
authors.initials: JH
authors.lastname: Tong
authors.forename: Z-Q
authors.initials: ZQ
authors.lastname: Zhou
authors.forename: M-L
authors.initials: ML
authors.lastname: Duan
authors.forename: J-G
authors.initials: JG
authors.lastname: Xu
authors.forename: H-J
authors.initials: HJ
authors.lastname: Zeng
authors.forename: S-H
authors.initials: SH
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014147:Tramadol / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000701:Analgesics, Opioid; D018341:Receptors, Adrenergic, alpha-2; D014147:Tramadol