GABA及GABA_A受体激动剂对胰腺癌细胞增殖及MMP-2表达的影响

Effect of GABA and GABA_A receptor activator on the proliferation of pancreatic cancer cells and the expression of MMP-2 in cancer cells

目的:探讨γ-氨基丁酸(γ-aminobutyric acid,GABA)及其A受体激动剂THIP对胰腺癌SW1990细胞系增殖及表达基质金属蛋白酶-2(MMP-2)的调控作用.方法:MTT法检测SW1990细胞的生长;免疫共聚焦技术观察不同浓度GABA(80、160、320μmol/L)、GABA(80μmol/L)+THIP(20、40、80μmol/L)作用细胞后MMP-2表达强度;通过荧光定量PCR(real-timePCR)检测MMP-2mRNA的表达.结果:GABA、THIP作用细胞后,均能促进其生长,且呈剂量依赖性,GABA组与对照组比差异显著(P<0.01或0.05);与对照组比较,GABA、THIP作用后细胞中MMP-2的表达明显增强(60.15±4.16,66.28±4.27,71.23±4.30vs26.04±4.54;75.01±4.64,80.86±4.67,86.35±4.89vs26.04±4.54,P<0.01或0.05),MMP-2mRNA表达也明显增强(39.35±3.24,52.46±4.16,63.45±5.12vs7.34±2.75;78.3±5.39,84.27±7.64,97.38±6.64vs7.34±2.75,P<0.01或0.05).结论:GABA可能是通过A受体介导胰腺癌SW1990细胞增殖,并通过促进MMP-2蛋白的表达来影响胰腺癌SW1990细胞的侵袭和转移.

AIM： To investigate the influence of γ-aminobutyric acid （GABA） and GABAA receptor activator on proliferation of pancreatic cancer cells and the expression of matrix metalloproteinase-2 （MMP-2） in cancer cells. METHODS： The effect of GABA, THIP on proliferation of pancreatic cancer cell line SW-1990 was investigated using MTT assay, and the effect of different concentrations of GABA （80, 160, 320 μmol/L） and GABA （80 μmol/L） ± THIP （20, 40, 80 μmol/L） receptor activator on the expression of MMP-2 in cancer cells was explored. The expression of MMP-2 protein was determined using Real-time quantitative PCR. RESULTS： GABA and THIP promoted the proliferation of SW-1990 cell and showed a dosedependent manner. Compared with the control group, cells were promoted by GABA and THIP significantly （P 〈 0.01 or 0.05）. Compared with the control group, the expression of MMP-2 in SW-1990 cell was promoted by GABA, THIP significantly （60.15 ± 4.16, 66.28 ± 4.27, 71.23 ± 4.30 vs 26.04 ± 4.54; 75.01 ± 4.64, 80.86 ± 4.67, 86.35 ± 4.89 vs 26.04 ± 4.54, P 〈 0.01 or 0.05）, and the expression of MMP-2 mRNA was increased markedly （39.35 ± 3.24, 52.46 ± 4.16, 63.45 ± 5.12 vs 7.34 ± 2.75; 78.3 ± 5.39, 84.27 ± 7.64, 97.38 ± 6.64 vs 7.34 ± 2.75, P 〈 0.01 or 0.05）. CONCLUSION： GABA could promote the proliferation of SW-1990 cell probably through GABAA receptor, GABA can promote SW-1990 cell invasion through up-regulating expressions of MMP-2.