title: Ethanol Promotes Cell Migration via Activation of Chloride Channels in Nasopharyngeal Carcinoma Cells.
abstract: BACKGROUND
  Excessive alcohol consumption has been identified as a significant risk factor for cancer development. Chloride channels have been proved previously by us and others to be involved in cancer cell migration. However, it is unknown whether chloride channels are associated with the effects of ethanol (EtOH) on cancer cell activities.
  
  
  METHODS
  The effects of EtOH on migration were detected by the wound healing assay in the nasopharyngeal carcinoma cells (CNE-2Z) and the normal nasopharyngeal epithelial cells (NP69-SV40T). The whole-cell patch clamp technique was used to record the EtOH-induced chloride current. The characteristics of the current were studied by anion substitution, hypertonic challenges, and channel blockers.
  
  
  RESULTS
  EtOH promoted the migration of cancerous CNE-2Z cells, but could hardly affect the migration of normal NP69-SV40T cells. The EtOH-induced migration could be inhibited by the chloride channel blockers, 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen. The exposure of CNE-2Z cells to EtOH activated a chloride current, with the ion selectivity of I(-) >Br(-) > Cl(-) >gluconate, demonstrated by ion substitution experiments. EtOH could still activate a similar chloride current in the absence of Ca(2+) in the medium. The current could be inhibited by the hypertonicity-induced cell shrinkage and the channel blockers NPPB and tamoxifen. EtOH could also activate a chloride current in normal NP69-SV40T cells, with the properties similar to those in CNE-2Z cells, but the current density was much smaller than that recorded in cancerous CNE-2Z cells.
  
  
  CONCLUSIONS
  It has been demonstrated in this study that EtOH can activate chloride channels and promote cell migration in cancerous cells, but can hardly affect the activities in normal cells. The data suggest for the first time that EtOH may promote cell migration via activation of chloride channels; long-term exposure to EtOH may increase the incident of tumor metastasis.
authors.affiliation: Department of Physiology , Medical College, Jinan University, Guangzhou, China.|Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Rongcheng Hospital, Rongcheng, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Physiology , Medical College, Jinan University, Guangzhou, China.|Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Wanhong
authors.initials: W
authors.lastname: Zuo
authors.affiliation: Department of Physiology , Medical College, Jinan University, Guangzhou, China.|Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Physiology , Medical College, Jinan University, Guangzhou, China.|Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Medical College, Jinan University, Guangzhou, China.|Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Shanwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Physiology , Medical College, Jinan University, Guangzhou, China.
authors.forename: Long
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Physiology , Guangdong Medical College, Zhanjiang, China.
authors.forename: Aihui
authors.initials: A
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom.
authors.forename: Tim J C
authors.initials: TJ
authors.lastname: Jacob
authors.affiliation: Department of Physiology , Medical College, Jinan University, Guangzhou, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
mesh_terms: D002277:Carcinoma; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D018118:Chloride Channels / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D000431:Ethanol
keywords: Cell Migration; Chloride Channels; Ethanol; Patch Clamp Techniques