洛伐他汀对胆管癌细胞株QBC939生长侵袭的抑制作用  

Lovastatin inhibits cell proliferation and migration in cholangiocarcinoma cell line QBC939

作　　者：刘磊[1] 龚彪[1] 别里克[1] 郝立校[2] 黄李雅[1] 蒋唯松[1] 

机构地区：[1]上海交通大学附属瑞金医院消化内科,200025 [2]解放军第四五五医院肝胆外科

出　　处：《中华肝胆外科杂志》2012年第4期296-301,共6页Chinese Journal of Hepatobiliary Surgery

摘　　要：目的研究洛伐他汀（lovastatin）对人胆管癌细胞株QBC939生长、迁移、凋亡等生物学行为的影响，初步探讨其可能机制。方法应用四甲基偶氮唑盐法检测洛伐他汀作用后细胞增殖情况。流式细胞技术检测细胞凋亡率。细胞划痕实验观察细胞迁移能力改变。RT—PCR和Western 印迹法检测洛伐他汀作用前后人胆管癌细胞株QBC939中白细胞介素-6（IL-6）、丝氨酸／苏氨酸蛋白激酶B（protein kinase B，PKB／Akt）、血管内皮生长因子（VEGF）、基质金属蛋白酶-9（MMP-9）mRAN和Akt蛋白的表达。结果与对照组相比，洛伐他汀组胆管癌细胞相对活力明显降低（24h、48h、72h：F=173．05、159．66、577．87，均为P〈0．01）并具有浓度时间依赖性。洛伐他汀组较对照组细胞早期凋亡[（14．29±0．75）％比（5．61±0．85）％]、总凋亡[（35．48±1．13）％比（24．94±0．40）％]比例明显增加（均为P〈0．01）。细胞24h、48h平均迁移速率明显减慢（分别为10．94±3．07比24．17±3．31和10．96±2．45比18．65±0．94，均为P〈0．01）。洛伐他汀组中IL-6、Akt、VEGF、MMP-9mRNA和Akt蛋白的表达明显低于对照组（均为P〈0．05）。结论洛伐他汀可抑制胆管癌细胞的增殖、迁移并诱导其凋亡，可能与下调IL-6、Akt、VEGF、MMP-9的表达有关。Objective To investigate the effects of lovastatin, a widely used antilipemic agent, on cell proliferation, migration and apoptosis in human cholangiocarcinoma cell line QBC939 and explore its possible mechanism. Method After QBC939 cells were either incubated with lovastatin alone or without it as a control, the methylthiazolyl tetrazolium assay （MTT） assay was used to detect cell proliferation at the 24 h, 48 h and 72 h mark flow cytometry （FCM） measured apoptosis at 48 b; scratch assay was used to determine cell migration at 48h; RT-PCR and Western blot detected the expression of inflammatory cytokine interleukin-6 （IL-6）, protein kinase （PKB/Akt）, vascular endothelial growth factor （VEGF）, matrix metalloproteinase-9 （MMP-9） mRNA and Akt protein at 48 h. Results Lovastatin significantly inhibited cell proliferation in a dose and time dependent manner （24 h, 48 h and 72 h： F：173.05, 159.66, 577.87 respectively, all P〈0.01）. After lovastatin treatment, apoptosis induction increased （t = 15.28, P〈0.01） as did early apoptosis （t = 13.24, P〈0. 01）, while the average migration velocity was reduced （24 h and 48 h： t= 6.21,5.95, respectively, all P〈0.01）. The Akt protein expression and mRNA expression of IL-6, Akt, VEGF, and MMP-9 were down-regulated after lovastatin treatment. Conclusions Lovastatin can inhibit cell proliferation, migration and promote apoptosis in human cholangiocarcinoma cell line QBC939. The mechanisms of suppression may be associated with down-regulation of IL-6, Akt, VEGF and MMP-9 expression.

关 键 词：胆管癌 洛伐他汀 增殖 迁移 细胞凋亡 

分 类 号：R735[医药卫生—肿瘤]