曲古抑菌素A对低氧肺腺癌细胞株A549HIF-1α、VEGF表达的影响  

Effect of Trichostatin A on the Expression of HIF-1α and VEGF in Lung Adenocarcinoma Cell Line A549 under Hypoxic Condition

作　　者：黄宏[1] 张珍祥[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院呼吸内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2008年第2期174-177,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的探讨组蛋白去乙酰化酶1抑制剂曲古抑菌素A(trichostain A,TSA)对低氧条件下人肺腺癌细胞株A549缺氧诱导因子1α(hypoxia induced factor 1α,HIF-1α)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法实验分为:常氧组(对照组)及低氧组(实验组),其中低氧组设4组,即低氧6 h组,低氧6 h前加TSA(1.25μg/ml)组,低氧24 h组,低氧24 h前加TSA(1.25μg/ml)组。运用免疫组织化学,RT-PCR方法检测HIF-1α、VEGF蛋白质和mRNA的表达。结果人肺腺癌细胞株A549在低氧6 h和24 h组HIF-1α、VEGF蛋白质和mRNA的表达较常氧组明显增强(P<0.05),TSA减弱低氧6 h和24 h组HIF-1α、VEGF蛋白质和mRNA的表达(P<0.05)。结论组蛋白去乙酰化酶1参与低氧人肺腺癌细胞血管生成的调节,TSA可能降低低氧条件下肺腺癌新生血管的生成。Objective To investigate the effect of trichostatin A （TSA） on the expression of HIF-1α and VEGF in lung adenocarcinoma cell line A549 under hypoxic condition. Methods The A549 cells were divided into normoxia group （control group） and hypoxia groups （experimental group） ： hypoxia 6 h group, group of TSA （1.25 μg/ml）＋hypoxia 6 h, hypoxia 24 h group and group of TSA （1.25 μg/ml）＋hypoxia 24 h. The expression of HIF-1α and VEGF was detected by using immunohistochemistry and reverse transcription-polymerase chain reaction （RT-PCR）. Results The expression of HIF-1α and VEGF mRNA and protein was increased significantly in hypoxia 6 h and 24 h groups as compared with normoxia group （P〈0.05）. TSA could significantly reduce the expression of HIF-1α and VEGF mRNA and protein （P〈0.05） in vitro. Conclusion Histone deacetylase 1 is involved in the tumor neovascularization in A549 cells and TSA can inhibit the angiogenesis by down-regulating the expression of HIF-1α and VEGF.

关 键 词：曲古抑菌素A 组蛋白去乙酰化酶1 肺腺癌 缺氧诱导因子1Α 血管内皮生长因子 

分 类 号：R734.2[医药卫生—肿瘤]