title: Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor.
abstract: OBJECTIVE
  To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC.
  
  
  METHODS
  The expression levels of GABA receptor subunit genes in various HCC cell lines and patients' tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer.
  
  
  RESULTS
  The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABAA receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo.
  
  
  CONCLUSIONS
  These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.
authors.forename: Zhi-Ao
authors.initials: ZA
authors.lastname: Chen
authors.forename: Mei-Yan
authors.initials: MY
authors.lastname: Bao
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Xu
authors.forename: Ruo-Peng
authors.initials: RP
authors.lastname: Zha
authors.forename: Hai-Bing
authors.initials: HB
authors.lastname: Shi
authors.forename: Tao-Yang
authors.initials: TY
authors.lastname: Chen
authors.forename: Xiang-Huo
authors.initials: XH
authors.lastname: He
keywords: hepatocellular carcinoma; invasion; migration; receptor; γ-aminobutyric acid (GABA)