内皮素3上调黑素瘤细胞株A375表达骨桥蛋白的研究  

Endothelin 3 upregulates the expression of osteopontin in human melanoma cells A375

作　　者：黄长征[1] 田进[1] 陶娟[1] 刘业强[1] 李延[1] 杨凌云[1] 张晶[1] 陈思远[1] 钱悦[1] 沈关心[2] 李家文[1] 涂亚庭[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院皮肤科,武汉430022 [2]华中科技大学同济医学院免疫学系

出　　处：《中华皮肤科杂志》2007年第10期631-633,共3页Chinese Journal of Dermatology

基　　金：国家自然科学基金(30671891)

摘　　要：目的探讨内皮素受体(ETR)-B拮抗剂BQ788和磷脂酰肌醇-3激酶(PI3K)抑制剂LY294002对黑素瘤细胞株A375骨桥蛋白基因的表达。方法对照组在人A375细胞培养体系中加入100 nmol/L内皮素3,试验组除加入100 nmol/L内皮素3外,分别加入1μmol/L BQ788和20μmol/L、50μmol/L LY294002,采用RT-PCR和蛋白质印迹方法检测骨桥蛋白的mRNA和蛋白表达。结果ETR-B拮抗剂BQ788和PI3K抑制剂LY294002均能显著减少人恶性黑素瘤细胞株A375中骨桥蛋白mRNA和蛋白的表达,与对照组比较,差异均有统计学意义(P<0.05)。高浓度较低浓度LY294002对骨桥蛋白表达的抑制作用更明显(P<0.05)。结论内皮素3/ETR-B能通过激活PI3K信号通路上调骨桥蛋白的表达。Objective To investigate the effect of endothelin receptor B （ ETR-B ） antagonist, BQ788, and phosphatidylinositol-3 kinase （ PI3K ） inhibitor, LY294002, on the gene expression ofosteopontin （ OPN ） in human melanoma cells A375. Methods A375 cells were cultured, and pretreated with 1 μmol/L BQ788, 20 μmol/L and 50 μmol/L LY294002, respectively, for 1 h before the addition of 100 nmol/L endothelin 3 （ ET-3 ） into the medium. Cells treated only with ET-3 served as the control. The mRNA and protein expressions of OPN were detected by RT-PCR and Western blot respectively. Results The mRNA and protein expressions of OPN were significantly decreased in A375 cells treated with BQ788, and in those treated with LY294002, as compared to those in the control cells （ all P 〈 0.05 ）. The inhibitory effect of LY294002 at higher concentrations was more significant than that at lower concentrations （ P 〈 0.05 ）. Conclusion ET3/ETR-B axis could upregulate the expression of OPN via activating the PI3K pathway in A375 cells.

关 键 词：黑色素瘤 受体 内皮素B 内皮缩血管肽 A375 骨桥蛋白 

分 类 号：R739.5[医药卫生—肿瘤]