洛伐他汀联合KRN633对胆管癌细胞株QBC939生物学行为的影响  

Effects of Lovastatin combined with KRN633 on cholangiocarcinoma cell line QBC939

作　　者：刘磊[1] 龚彪[1] 别里克[1] 许斌[1] 郝立校[2] 蒋唯松[1] 刘渊[1] 

机构地区：[1]上海交通大学附属瑞金医院消化科,上海200025 [2]中国人民解放军455医院

出　　处：《胃肠病学和肝病学杂志》2011年第11期1054-1059,共6页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的研究洛伐他汀(Lovastatin)联合血管内皮生长因子受体酪氨酸激酶抑制剂(KRN633)对人胆管癌细胞株QBC939生长、迁移、凋亡等生物学行为的影响。方法应用四甲基偶氮唑盐(MTT)法检测不同药物浓度作用24 h、48 h、72 h后细胞增殖情况;倒置显微镜下观察细胞形态学改变;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法检测药物作用前后髓样细胞白血病-1(Mcl-1)、丝氨酸/苏氨酸蛋白激酶B(Akt)、肿瘤坏死因子相关凋亡诱导配体(TRAIL)、血管内皮生长因子(VEGF)的表达。结果洛伐他汀、KRN633能明显抑制QBC939细胞的增殖(P<0.01)并呈浓度-时间依赖性,洛伐他汀联合KRN633具有协同抑制效应(F=8.85,P<0.05)。药物作用下可观察到QBC939细胞呈现凋亡形态学改变;流式细胞学结果显示细胞凋亡率明显增加[(37.5±1.92)%、(32.14±1.30)%、(11.23±1.26)%,F=250.04,P<0.01]。联合用药组细胞24 h、48 h平均迁移速率明显减慢(分别为1.21±0.68和1.52±0.19,P<0.05)。生长增殖、凋亡、迁移相关基因Mcl-1、Akt、VEGF mRNA的表达明显低于对照组(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,与KRN633联合应用具有协同抑制效应。Objective To investigate the effects of Lovastatin combined with KRN633, a selective inhibitor of vascu- lar endothelial growth factor receptor-2 tyrosine kinase on cell proliferation, migration and apoptosis in human cholangio- carcinoma cell line QBC939. Methods After QBC939 cells were incubated with Lovastatin alone or in combination with KRN633, the proliferation of QBC939 cells was measured by methyl thiazolyl tetrazolium （MTT） assay; morpholog- ic changes and apoptosis were observed under optical microscope and flow cytometry （FCM） ; cell migration was deter- mined by scratch assay. The expression of myeloid cell leukemia-1 （ Mcl-1 ） , protein kinase B （Akt） , tumor necrosis factor-related apoptosis-inducing ligand （TRAIL）, vascular endothelial growth factor （VEGF） mRNA were detected by RT-PCR. Results Lovastatin and KRN633 significantly inhibited cell proliferation in a dose-and time-dependent man- ner （P 〈 0. 01 ） , and the combination effect was even stronger. Apoptotic cells and morphologic changes could be found under optical microscope; the FCM revealed that Lovastatin incorporation with KRN633 could markedly upgrade the ap- optosis rate and reduce the average migration velocity. The expression of Mcl-1, Akt and VEGF mRNA were down-regu- lated, while expression of TRAIL mRNA was up-regulated after lovastatin and KNR633 treatment. Conclusion Lovas- tatin combined with KRN633 can inhibit cell proliferation, migration and induce apoptosis in human cholangiocarcinoma cell line QBC939. Lovastatin and KRN633 have synergistic effects in QBC939 cells.

关 键 词：胆管癌 洛伐他汀 血管内皮生长因子受体抑制剂 血管内皮生长因子 细胞增殖 细胞迁移 细胞凋亡 

分 类 号：R735.8[医药卫生—肿瘤]