Brief Article
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World J Gastroenterol. Jun 7, 2012; 18(21): 2704-2711
Published online Jun 7, 2012. doi: 10.3748/wjg.v18.i21.2704
GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit
Yue-Hui Li, Yan Liu, Yan-Dong Li, Yan-Hong Liu, Feng Li, Qiang Ju, Ping-Li Xie, Guan-Cheng Li
Yue-Hui Li, Yan Liu, Yan-Dong Li, Yan-Hong Liu, Feng Li, Qiang Ju, Ping-Li Xie, Guan-Cheng Li, Cancer Research Institution, Central South University, Changsha 410078, Hunan Province, China
Yue-Hui Li, Yan Liu, Yan-Dong Li, Yan-Hong Liu, Feng Li, Qiang Ju, Ping-Li Xie, Guan-Cheng Li, Key Laboratory of Carcinogenesis, Ministry of Health, Changsha 410078, Hunan Province, China
Yue-Hui Li, Yan Liu, Yan-Dong Li, Yan-Hong Liu, Feng Li, Qiang Ju, Ping-Li Xie, Guan-Cheng Li, Key Laboratory of Carcinogenesis and Invasion, Ministry of Education, Changsha 410078, Hunan Province, China
Author contributions: Li YH and Li GC designed the research and wrote the paper; Liu Y, Li YD, Liu YH, Li F, Ju Q and Xie PL performed the research and analyzed the data.
Supported by The Innovation Fund of Central South University, No. 234077231
Correspondence to: Guan-Cheng Li, PhD, Professor, Tumor Immunobiology Laboratory of Cancer Research Institute, Central South University, Changsha 410078, Hunan Province, China. libsun@163.com
Telephone: +86-731-84805445 Fax: +86-731-82355042
Received: December 15, 2011
Revised: February 2, 2012
Accepted: March 9, 2012
Published online: June 7, 2012
Abstract

AIM: To investigate the function of gamma-aminobutyric acid (GABA) and gamma-aminobutyric acid A receptor θ subunit (GABRQ) in hepatocellular carcinoma (HCC).

METHODS: Semiquantitative polymerase chain reaction was used for detecting the expression of GABRQ receptor among HCC cell line HepG2, normal liver cell line L-02, non-malignant Chang’s liver cells, 8 samples of HCC tissues and paired non-cancerous tissues. HepG2 cells were treated with GABA at serial concentrations (0, 1, 10, 20, 40 and 60 μmol/L), and their proliferating abilities were analyzed with the methyl thiazolyl tetrazolium assay, cell cycle analysis and tumor implanted in nude mice. Small interfering RNA was used for knocking down the endogenous GABRQ in HepG2. Proliferating abilities of these cells treated with or without GABA were analyzed.

RESULTS: We identified the overexpression of GABRQ in HCC cell lines and half of the tested HCC tissues. Knockdown of endogenous GABRQ expression in HepG2 attenuated HCC cell growth, suggesting its role in HCC cell viability. We studied the effect of GABA in the proliferation of GABRQ-positive cell lines in vitro and in vivo, and found that GABA increased HCC growth in a dose-dependent manner. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRQ-expressing HepG2 cells, but not GABRQ-knockdown HepG2 cells, which means that GABA stimulates HepG2 cell growth through GABRQ.

CONCLUSION: GABRQ play important roles in HCC development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of HCC.

Keywords: Hepatocellular carcinoma; Proliferation; Gamma-aminobutyric acid; Gamma-aminobutyric receptor θ; small interfering RNA