Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor

• Main Authors: Zhi-ao Chen, Mei-yan Bao, Yong-fen Xu, Ruo-peng Zha, Hai-bing Shi, Tao-yang Chen, Xiang-huo He
• Format: Article
• Language: English
• Published: China Anti-Cancer Association 2012-06-01
• Series: Cancer Biology & Medicine
• Subjects: γ-aminobutyric acid (GABA); receptor; migration; invasion; hepatocellular carcinoma
• Online Access: http://www.cancerbiomed.org/index.php/cocr/article/view/56

<b>Objective</b> 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.<br><b>Methods</b> 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 <i>in vivo</i> orthotopic model of liver cancer.<br><b>Results</b> 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 <i>in vivo</i>.<br><b>Conclusions</b> These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system.