摘要
目的观察抑制性神经递质γ-氨基丁酸(GABA)对人胆管癌细胞株QBC939生物学行为的影响。方法采用MTY比色法观察GABA对人系胆管癌细胞QBC939增殖的作用,PCR—ELISA法观察其对QBC939细胞端粒酶活性的影响,Transwell小室分析GABA对胆管癌细胞侵袭能力的影响,逆转录聚合酶链反应(RT—PCR)、明胶酶谱法分析GABA对QBCQBC939细胞分泌的基质金属蛋白酶(matrix metalloproteinase, MMP) mRNA和酶活性的影响,数据采用单因素方差分析和Dunnett法处理。结果GABA对人胆管癌细胞QBC939的增殖有抑制作用(抑制率由2.6%增至26.8%,P〈0.05);抑制癌细胞中端粒酶的活性(0.82±0.05)vs.(0.56±0.05)(P〈0.05);抑制胆管癌细胞穿透Matrigel胶的能力(在100μmol/L浓度的GABA作用下,穿透细胞数由(60±10)个降至(43±4)个(P〈0.05),同时胆管癌细胞分泌的基质蛋白酶MMP-2和MMP-9的mRNA和活性下降,这三种效应均成浓度依赖性。结论GABA抑制胆管癌细胞QBC939的生长并减弱侵袭转移能力,其机制可能与其抑制端粒酶活性和基质蛋白酶MMP-2和MMPO的分泌和活性有关。
Objective To explore the effect of GABA on the bionomics of cholangiocarcinoma cell QBC939. Methods The proliferation of QBC939 cells was investigated by MTT. The telomerase activity of QBC939 cells was examined by modified PCR-ELISA assay. Transwell cell culture chamber assay in vitro was used to detect the ability of invasion of cholangiocarcinoma QBC939. The expression of matrix metalloproteinase (MMP) mRNA and enzymatic activity of QBC939 cells were detected by reverse transcription polymerase chain reaction(RT-PCR) and gelatin zymography, respectively. Results GABA at all tested concentration inhibited the growth and proliferation of QBC939 cells in a time-independent manner,Telomerase activity was inhibited by GABA [ ( 0. 82 ± 0. 05 ) vs. ( 0. 56 ±0. 05 ), ( P 〈 0. 05 ) ]. GABA inhibited tumor cells' trans-Matrigel ability (at 100 μmol/L GABA, cell's number decreased from 60 ± 10 to 43 ± 4, P 〈 O. 05 ), and significantly inhibited the activity and expression of MMP( MMP-2, MMP- 9) in a dose dependent way. Conclusions GABA can inhibit the growth, invasion and metastasis of cbolangioearcinoma QBC939. The down-regulation of the activity of Telomerase and MMP may be involved in this mechanism.
出处
《中华普通外科杂志》
CSCD
北大核心
2008年第12期960-962,共3页
Chinese Journal of General Surgery
关键词
胆管肿瘤
肿瘤浸润
Γ-氨基丁酸
端粒酶
Bile duct neoplsms
Neoplasm invasiveness
Gamma-aminobatyric acid
Telomerase