GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit.
OBJECTIVE
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.


CONCLUSIONS
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.
Cancer Research Institution, Central South University, Changsha 410078, Hunan Province, China.
Yue-Hui
YH
Li
Yan
Y
Liu
Yan-Dong
YD
Li
Yan-Hong
YH
Liu
Feng
F
Li
Qiang
Q
Ju
Ping-Li
PL
Xie
Guan-Cheng
GC
Li
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D034741:RNA, Small Interfering; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid