title: Proliferative effects of gamma-amino butyric acid on oral squamous cell carcinoma cells are associated with mitogen-activated protein kinase signaling pathways.
abstract: Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult mammalian central nervous system, has been reported to play an important physiological role in peripheral non-neuronal tissues, such as tumors. However, whether deregulated GABA is associated with oral squamous cell carcinoma (OSCC) is currently unknown. In this study, we investigated the effects of GABA on the proliferation of the OSCC cell line, Tca8113. Immunohistochemical analyses were performed to examine the expression of GABA A type receptor pi subunit (GABRP) in human OSCC tissues, and reverse transcription polymerase chain reaction, immunofluorescence staining and western blot analysis were performed to examine the expression of GABRP in Tca8113 cells. The proliferative effects of GABA on Tca8113 cells were analyzed by CCK-8 assay and flow cytometry. The activation status of mitogen-activated protein kinases (MAPKs) was examined by western blot analysis. GABRP expression was observed in the cytoplasm with a higher level in poorly differentiated OSCC tissues. The mRNA and protein expression levels of GABRP were detected in the Tca8113 cells. The addition of GABA and the GABA A type receptor agonist, Muscimol, promoted cell proliferation and inhibited cell apoptosis through the activation of the p38 MAPK and the inhibition of the JNK MAPK signaling pathways. These results imply a novel role of GABA in OSCC.
authors.affiliation: Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ji
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Jinlin
authors.initials: J
authors.lastname: Song
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Luo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology*; D011963:Receptors, GABA-A / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D020928:Mitogen-Activated Protein Kinases