title: Propofol and bupivacaine in breast cancer cell function in vitro - role of the NET1 gene.
abstract: BACKGROUND
  It has been hypothesized that anaesthesia during primary breast cancer surgery may influence recurrence or metastasis. Effects of anaesthetic drugs on breast cancer cell function are unclear. The Neuroepithelial Cell Transforming Gene 1 (NET1) gene is associated with promoting migration in adenocarcinoma in vitro. Therefore, we investigated the role of NET1 in the effect of anaesthetic drugs propofol and bupivacaine on breast cancer cell function in vitro.
  
  
  METHODS
  Estrogen receptor-negative (ER-negative) MDA-MB-231 and ER-positive MCF7 breast cancer cells were incubated with propofol (1-10 μg/ml) and bupivacaine (0.5-100 μg/ml) or control medium. Cell functions were determined with the CellTiter 96 Aqueous One Solution Cell Proliferation Assay, Chemotaxis 96-well Cell Migration and Invasion Assay. NET1 gene expression was determined by real-time PCR with gene silencing using siRNA and stimulation by lysophosphatidic acid (LPA).
  
  
  RESULTS
  Propofol did not reduce breast cancer cell proliferation of MCF7 or MDA-MB-231 cells. However, it did reduce migration of both MCF7 and MDA-MB-231 cells which was reversed by silencing NET1. Propofol reduced invasion of MCF7 but not of MDA-MB-231 cells, which was unaffected by siRNA. Propofol reduced expression of NET1 by 42-88% in MCF7 and by 49-79% in MDA-MB-231 cells. Bupivacaine had no significant effect on breast cancer cell function or NET1 expression.
  
  
  CONCLUSIONS
  Propofol reduced NET1 expression and cell migration in both ER-positive and -negative cells, which was reversed by silencing NET1, implying a role for NET1 in mediating the effect of propofol on breast cancer cell function in vitro.
authors.affiliation: Department of Anaesthesia, Mater Misericordiae University Hospital, School of Medicine & Medical Science University College Dublin, Ireland donal.buggy@ucd.ie.
authors.forename: Patricija
authors.initials: P
authors.lastname: Ecimovic
authors.forename: David
authors.initials: D
authors.lastname: Murray
authors.forename: Peter
authors.initials: P
authors.lastname: Doran
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Buggy
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002045:Bupivacaine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; C099763:NET1 protein, human; D015513:Oncogene Proteins; D012333:RNA, Messenger; D002045:Bupivacaine; D015742:Propofol
keywords: MCF7; MDA-MB-231; NET1 gene; Propofol; breast cancer cells; bupivacaine; cell migration