法尼酯X受体激动剂GW4064对人胆管癌细胞株QBC939生长的影响  

The Effect of FXR Agonist GW4064 on Growth of Human Cholangiocarcinoma Cell Line QBC939

作　　者：张银新[1] 戴佳奇[1] 王坚[1] 

机构地区：[1]上海交通大学医学院附属仁济医院普外科,上海200127

出　　处：《外科理论与实践》2010年第4期412-415,共4页Journal of Surgery Concepts & Practice

基　　金：上海市科学技术委员会科研计划项目(07ZR14073)

摘　　要：目的:研究法尼酯X受体(FXR)激动剂GW4064对人胆管癌细胞株QBC939增殖和凋亡的影响,并检测QBC939细胞株中FXR基因表达的改变。方法:用浓度为0.5、1.0和5.0μmol/L的法尼酯X受体(FXR)激动剂GW4064刺激人胆管癌细胞株QBC939,用四甲基偶氮唑蓝(MTT)比色法检测24、48 h后细胞活力的变化,以流式细胞仪技术检测药物刺激48 h后肿瘤细胞凋亡的变化,并以RT-PCR检测QBC939细胞株中FXR mRNA表达的改变。结果:浓度为1.0、5.0μmol/L的GW4064在作用24 h后即能显著抑制胆管癌细胞生长(P<0.05);在药物作用48 h后,所有浓度的GW4064均能对肿瘤细胞生长起明显的抑制作用(P<0.05)。流式细胞仪检测细胞凋亡的结果显示,药物刺激48 h后,对照组凋亡细胞占细胞总数的3.38%,加入0.5μmol/L浓度GW4064的细胞凋亡率为10.02%;而加入1.0和5.0μmol/L浓度的GW4064后,细胞凋亡率明显升高至23.74%和42.11%。RT-PCR结果显示,所有浓度的GW4064于刺激48 h后,QBC939细胞株中FXR基因表达增加,与对照组相比均有统计学差异(P<0.05)。结论:GW4064能通过特异性激动FXR有效抑制胆管癌细胞株QBC939的细胞活力,并促进其凋亡,这一过程可能与其上调FXR的表达有关。Objective To investigate the role that GW4064 plays as the agonist of farnesiod X receptor（FXR） in the regulation of proliferation and apoptosis of the human cholangiocarcinoma cell line QBC939.Method The QBC939 cells were exposed to various concentrations of GW4064（ranged from 0.5-5.0 μmol/L）,the synthetic specific agonist of FXR,for 24 or 48 hours.Cell viability was evaluated with the MTT test.Apoptotic cells were assessed by flow cytometric（FCM） analysis with an AnnexinV-FITC Detection Kit.Real-Time PCR was used to measure the mRNA expression level of FXR.Results GW4064 treatment for 24 h with the concentrations of 1.0 and 5.0 μmol/L caused a dose-dependent decrease of cell viability（P0.05）.All the treatment groups showed significant decrease of cell viability after 48 h（P0.05）.FCM analysis showed the apoptotic rates of the groups treated by the GW4064 for 48 h at the concentrations of 0.5,1.0 and 5.0 μmol/L,were 10.02%,23.74% and 42.11% respectively,each showed a significant increase as compared to the control group.The mRNA level of FXR in all the treatment groups was increased after exposure for 48 h,and showed statistically significant difference compared to the control group（P〈0.05）.Conclusions The activation of FXR by its specific agonist GW4064 exerts inhibition of cell viability and apoptotic effect on the QBC939 cell line.These effects are probably related with the up-regulation of the genetic expression of FXR.

关 键 词：胆管肿瘤 法尼酯X受体 GW4064 细胞生长 

分 类 号：R735.8[医药卫生—肿瘤]