利用人结肠癌细胞株HCT116细胞为研究模型，探究γ-氨基丁酸B型受体（GABABR）/糖原合成激酶3β（GSK-3β）/核转录因子（NF-κB）信号通路对结肠肿瘤细胞HCT116周期的影响，明确GABABR调控结肠癌细胞增殖的机制。

使用人结肠癌细胞株HCT116细胞为模型，构建针对GABABR的shRNA，流式细胞仪检测不同刺激条件下HCT116细胞周期分布，四甲基偶氮唑盐微量酶反应比色法（MTT）、5-溴脱氧尿嘧啶核苷（Brdu）法检测细胞的增殖能力变化。

GABABR可调控HCT116细胞的增殖。GABABR激动剂巴氯芬将HCT116细胞滞留在G1期，GSK-3β激动剂wort能逆转巴氯芬对结肠癌的该作用；GSK-3β抑制剂SB216763处理后，HCT116细胞增殖得到抑制，而NF-κB激动剂PMA可以阻断此作用；NF-κB激动剂PDTC能够回救敲低GABABR所引起的HCT116细胞增殖抑制，Akt抑制剂MK-2206 2HCl能逆转巴氯芬、SB216763对HCT116细胞增殖的抑制作用。

GABABR/GSK-3β/NF-κB信号通路可以调控结肠癌细胞增殖，通过抑制GSK-3β的活性，抑制NF-κB信号通路的激活，将HCT116细胞滞留在G1期。GABABR/GSK-3β/NF-κB信号通路可以作为临床预防和治疗结肠癌的潜在药物靶点之一。

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.

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.

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.

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.