Baclofen, a GABAB receptor agonist, inhibits human hepatocellular carcinoma cell growth in vitro and in vivo.

Gamma aminobutyric acid (GABA) has been reported to affect cancer development, but the activation of its type B receptor (GABABR) has shown contradictory effects on the progress of human carcinoma. In this study, we investigated the antitumor effect of the GABABR agonist baclofen (Bac) on growth of human hepatocellular carcinoma (HCC) in vitro and in vivo. We found Bac induced G(0)/G(1) phase arrest which was associated with down-regulation of intracellular cAMP level, and up-regulation of p21(WAF1) protein expression as well as its phosphorylation level. These in vitro effects could be abrogated by pretreatment with the specific GABABR antagonist phaclofen (Pha). Moreover, systemic administration of Bac significantly suppressed Bel-7402 xenograft tumor growth. Our data support the inhibitory effect of GABABR activation on HCC development, which would raise the possibility to develop Bac as a therapeutic drug for the treatment of HCC.