罗格列酮对前列腺癌细胞血管生成拟态的影响  

Effect of rosiglitazone on vasculogenic mimicry in prostate cancer cell line PC-3

作　　者：秦亮[1] 陈安民[1] 郭风劲[1] 杨卿[1] 任晔[1] 徐飞[1] 廖晖[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院骨科,武汉430030

出　　处：《骨科》2015年第6期285-289,共5页ORTHOPAEDICS

基　　金：教育部新教师基金项目(200804871051);湖北省卫生厅青年人才基金(QJX2010-5)

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)配体罗格列酮(rosiglitazone,RGZ)对前列腺癌PC-3细胞血管生成拟态的影响。方法体外培养人前列腺癌PC-3细胞,应用细胞增殖与毒性检测(Cell Counting Kit-8,CCK-8)法观察罗格列酮不同浓度和不同作用时间对前列腺癌PC-3细胞增殖的影响;体外建立matrigel三维培养系统,观察罗格列酮对PC-3细胞血管生成拟态(vasculogenic mimicry,VM)形成的影响;应用RT-qPCR和ELISA的方法检测血管内皮钙黏蛋白(vascular endothelial cadherin,VE-cadherin)、EphA2、血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA和VEGF蛋白的表达。结果罗格列酮在48 h后明显抑制前列腺癌PC-3细胞增殖,且呈时间和剂量依赖性。前列腺癌PC-3细胞在体外三维培养条件下能够形成环状和网络样结构。罗格列酮能够抑制PC-3细胞VEGF、VE-cadherin、EphA2 mRNA及VEGF蛋白的表达,并使其形成血管生成拟态的能力明显降低。结论罗格列酮可能通过下调前列腺癌细胞VEGF、VE-cadherin、EphA2的表达抑制血管生成拟态形成。Objective To investigate the effect of rosiglitazone （RGZ）, the tigand of peroxisome proliferator-activated receptor 7 （PPARy）, on vasculogenic mimicry in human prostate cancer cell line PC-3 in vitro and to reveal the related molecular mechanisms. Methods PC-3 cells were cultured in vitro. The effect of RGZ with different concentrations （0. 1, 1.0 and 10. 0 μmol/L） and different action durations （1 to 6 days） on the growth of PC-3 cells was detected by Cell Counting Kit-8 （CCK-8） assay. A 3-dimensional cell culture system for PC-3 cells was established to observe vasculogenic mimicry formation. The change of vasculogenic mimicry formation under RGZ treatment was observed. Reahime- quantitative polymerase chain reaction （RT-qPCR） was used to detect the effect of RGZ on the mRNA expression of VEGF, VE-cadherin, and EphA2, respectively. The expression of VEGF protein was analyzed by ELISA. Results RGZ significantly inhibited the celt proliferation after 48 h in a dose- and time-dependent manner. PC-3 cells could form patterned matrix VM or tubular VM in 3-demintional cul- ture system. RGZ markedly reduced VM density or formed shorter tubular VM in 0. 1, 1.0, 10.0 μmol/L groups than in control group. After treatment with RGZ for 48 h, the expression levels of VEGF, VE-cadherin, and EphA2 mRNA were decreased in RST-treated group as compared with control group. Meantime, RGZ inhibited VEGF protein secretion, respectively. Conclusion The results indica- ted that activation of PPARy by RGZ can inhibit VM formation in PC-3 cells, which may be through down-regulation of the expression of VEGF, VE-cadherin and EphA2.

关 键 词：前列腺肿瘤 过氧化物酶体增殖物激活受体 罗格列酮 血管生成拟态 

分 类 号：R737.25[医药卫生—肿瘤]