γ-氨基丁酸抑制胆管癌细胞株QBC939增殖及其机制的研究

目的 观察γ-氨基丁酸(GABA)对胆管癌细胞QBC939增殖、凋亡和端粒酶活性的影响.方法 采用MTT比色法观察GABA对人系胆管癌细胞QBC939增殖的作用,流式细胞术检测GABA对胆管癌细胞QBC939凋亡的影响,PCR-ELISA法观察其对QBC939细胞端粒酶活性的影响,放射免疫分析法检测cAMP含量.结果 GABA抑制胆管癌细胞的增殖(抑制率由2.6%增至26.8%,P<0.05),促进细胞凋亡(凋亡率由4.8%增至28.03%,P<0.05),并且抑制癌细胞中端粒酶的活性(0.82±0.048 vs 0.56±0.054,P<0.05),同时促进胆管癌细胞内cAMP含量的增加[(0.59±0.049)nmol/L vs (0.82±0.033)nmol/L,P<0.05].结论 GABA可能通过受体后信息介导途径,诱导细胞凋亡,并抑制癌细胞端粒酶活性,从而抑制胆管癌细胞的增殖.

Study of inhibition of GABA on proliferation of cholangiocarcinoma cell line QBC939 and its mechanism

Objective To explore the effect of gamma-aminobutyric acid (GABA) on the growth, apoptosis and telomerase activity of Cholangiocarcinoma cell line QBC939. Methods Cholangiocarcinoma cell line QBC939 was cultured by routine method, and then treated with different concentrations of GABA (1-1000 μmmol/L). The proliferation, apoptosis and cell cycle of QBC939 cells was investigated by MTT, Flow cytometry and transmission electron microscopy. The telomer-ase activity of QBC939 cells was examined by modified PCR-ELISA assay. Radioimmunoassay was used to measure the intracellular cyclic adenosine monophosphate(cAMP) content. Results The dif-ferent concentrations of GABA inhibited the growth of QBC939 cells and promoted the apoptosis. The apop-totic rate of QBC939 cells was increased from 4. 8% to 28. 03%, which had significant difference (P<0.05). It had no effect for distribution of cell cycle. Cell nuclear condensation and apoptotic bodies were seen by transmission electron microscopy. Telomerase activity was inhibited by GABA(0. 82±0. 048 vs 0.56±0. 054, P<0.05). The content of intracellular cAMP was increased with the increase of GABA concentration in a dose-dependent manner [(0. 59±0. 049) nmol/L vs (0. 82±0. 033)nmol/L, P<0. 05]. Conclusion GABA can inhibit the proliferation of QBC939 cells by promoting apoptosis and inhibiting telomerase activi-ty, which may be mediated by the information transmission of post-receptor.