Proliferative effects of gamma-amino butyric acid on oral squamous cell carcinoma cells are associated with mitogen-activated protein kinase signaling pathways

Ma,Jing; Zhang,Yan; Wang,Jun; Zhao,Tianyu; Ji,Ping; Song,Jinlin; Zhang,Hongmei; Luo,Wenping

doi:10.3892/ijmm.2016.2597

Proliferative effects of gamma-amino butyric acid on oral squamous cell carcinoma cells are associated with mitogen-activated protein kinase signaling pathways

Authors:
- Jing Ma
- Yan Zhang
- Jun Wang
- Tianyu Zhao
- Ping Ji
- Jinlin Song
- Hongmei Zhang
- Wenping Luo
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Affiliations: Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, P.R. China, Stomatological Hospital of Chongqing Medical University, Chongqing 401147, P.R. China
Published online on: May 19, 2016 https://doi.org/10.3892/ijmm.2016.2597
Pages: 305-311

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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.

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