Effect of gamma aminobutyric acid type B receptor on the cycle of colon cancer HCT116 cell

Objective To investigate the regulating effect of gamma aminobutyric acid B receptor (GABABR)/glycogen synthase kinase 3β (GSK-3β)/NF-κB signaling pathway on cycle of colon cancer cell line HCT116 and to clarify the mechanism of GABABR regulating the increasing of colon cancer. Methods HCT116 cells were used as a model to construct shRNA targeting GABABR. Cell cycle distribution of HCT116 cell under different stimuli was detected by flow cytometry. MTT and Brdu assay were used to detect cell proliferation ability. Results GABABR could regulate the proliferation of HCT116 cells. Baclofen, the GABABR agonist, arrested HCT116 cells in G1 phase, while GSK-3β agonist wort could reverse this effect. After the treatment of GSK-3β inhibitor SB216763, the proliferation of HCT116 cells was inhibited, which could be blocked by NF-κB agonist PMA. NF-κB agonist PDTC saved the proliferation inhibition of HCT116 cells caused by low GABABR. Akt inhibitor MK-2206 2HCl reversed the inhibitory effect of baclofen and SB216763 on proliferation of HCT116 cells. Conclusions The GABABR/GSK-3β/NF-κB signaling pathway can regulate the proliferation of colon cancer cells, results in supression of GSK-3β, and NF-κB activation, and retain HCT116 cells in G1 stage. GABABR/GSK-3β/NF-κB signaling pathway may be one of the potential drug targets for the clinical prevention and treatment of colon cancer. Key words: Colonic neoplasms; Genes, tumor suppressor; Gamma aminobutyric acid type B receptor; GABABR/GSK-3β/NF-κB signaling pathway