目的：通过体内、体外实验，探讨γ-氨基丁酸（γ-aminobutyric acid，GABA）对结直肠癌SW480、HCT116细胞的抑制作用及其与化疗联用的增敏作用。方法：采用CCK-8方法分析GABA及其与抗癌药5-氟尿嘧啶（5-fluorouracil，5-FU）或奥沙利铂（Oxaliplatin，OXA）联用对结直肠癌SW480、HCT116细胞增殖的影响，流式细胞术分析GABA对SW480、HCT116细胞周期的影响。通过裸鼠成瘤实验观察移植瘤质量和体积，免疫组化法检测裸鼠肿瘤组织Ki67蛋白的表达，TUNEL染色观察裸鼠结直肠癌细胞的凋亡，体内实验研究GABA与OXA联用对肿瘤细胞生长的影响。结果：100 μmol/L GABA可显著抑制结直肠癌SW480、HCT116细胞的增殖，其抑制率分别为（37.38±2.62）%、（15.54±1.33）%，GABA浓度增加至200 μmol/L时，其抑制作用未见明显增强。GABA使SW480、HCT116细胞S期数量分别减少11.8%及10.7%。GABA与5-FU或OXA联用组对SW480细胞增殖抑制率高于5-FU或OXA组\[（72.76±1.07）% vs （63.82±3.29）%或（65.60±1.19）% vs （57.09±125）%；q=4.079或4.128，P<0.05\]，对HCT116细胞增殖抑制率也高于单用5-FU及OXA组\[（79.53±1.12）% vs（69.71±0.09）% 或（73.19±0.07）% vs（64.65±1.99）%；q=4.569或4.561，P<0.05\]。实验结束时，GABA与OXA联用组小鼠移植瘤质量、体积显著低于对照组和OXA组\[（0.20±0.016） vs （0.42±0.039）、（0.36±0.030）g和（250±27）vs （780±60）、（520±46）mm3，均P<0.01\]；抑制Ki67蛋白在肿瘤组织的表达、促进肿瘤组织细胞的凋亡。结论：GABA对结直肠癌细胞增殖具有较强的抑制作用，与5- FU或OXA联用可增强化疗效果。

Objective:To explore the inhibitory effect of γ-aminobutyric acid (GABA) on colorectal cancer cells (SW480 and HCT116 lines) and its chemosensitization. Methods: The effects of GABA and its combination with anticancer drugs 5-fluorouracil (5-FU) or oxaliplatin (OXA) on proliferation of colorectal cancer cells (SW480, HCT116) were determined using CCK-8 assay; the effects of GABA on cell cycles of SW480 and CT116 were analyzed using Flow cytometry assay; the tumor weight and size were investigated in experiment of tumor-bearing nude mice; the expression of Ki67 protein in cancer tissues of the nude mice and the apoptosis of colorectal cancer cells in the nude mice were observed using immunohistochemistry and TUNEL staining assays respectively; the effect of GABA combined with OXA on growth of the tumor cells was observed with experiment in vivo. Results: GABA (100 μmol/L) significantly inhibited the proliferation of SW480 and HCT116 cells, their inhibition rates were (37.38±262)% and (15.54±1.33)%, respectively. Further increasing of the GABA concentration to 200 μmol/L did not obviously enhance the inhibitory rate. GABA decreased the number of SW480 and HCT116 cells at S phase by 11.8% and 10.7%, respectively. Inhibitory rates of the ISW480 cell in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA groups (combined with 5-FU: \[72.76±1.07\]% vs \[63.82±3.29\]%, q=4.079, P<005; combined with OXA: \[65.60±1.19\]% vs \[57.09±1.25\]%, q=4.128, P<0.05); inhibitory rates of HCT116 cells in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA alone groups (combined with 5-FU: \[79.53±1.12\]% vs \[69.71±009\]%, q=4.569, P<0.05; combined with OXA: \[73.19±0.07\]% vs \[64.65±199\]%, q=4.561, P<005). At end of the experiment, the tumor weight and size of the nude miceinthe combined group of GABA and OXA were significantly lower than those in control group and the oxaliplatin alone group (\[0.20±0016\] g vs \[0.42±0.039\] g, \[0.36±0.030\]g; \[250±27\] mm3 vs \[780±60\] mm3, \[520±46\] mm3, P<0.01). The combination of GABA with OXA also significantly inhibited the expression of Ki67 protein in the tumor tissues and promoted apoptosis of the tumor cells in tumor tissues. Conclusion: GABA couldhave strong inhibitory effect on proliferation of the colorectal cancer cells and its combination use with 5-FU or OXA could enhance efficacy of chemotherapy.

国家自然科学基金资助项目（No.81472770）