TTF1对肿瘤血管生成的抑制作用

Inhibition of tumor angiogenesis by TTF1

[目的]探讨TTF1对肿瘤血管生成的抑制作用.[方法]建立人肝癌HepG-2细胞裸鼠移植瘤模型,取40只随机分为模型对照组、芹菜素组、小、中、大剂量(5,10,20μmol/g)TTF1组,药物干预21d后处死裸鼠;采用免疫组织化学方法检测CD34,以Weidner微血管计数法计算肿瘤微血管密度(MVD);应用Western-blot方法检测血管内皮生长因子(VEGF)、成纤维细胞生长因子(bFGF)、环氧合酶-2(COX-2)、缺氧诱导因子-1α(HIF-1α)和KDR.[结果]大、中、小剂量TTF1组MVD明显下降,肿瘤组织VEGF,KDR,bFGF,HIF-1α和COX-2蛋白的表达明显下调.[结论]TTF1对肿瘤血管生成有明显的抑制作用,其机制可能与下调VEGF,KDR,bFGF,HIF-1α和COX-2蛋白有关联.

OBJECTIVE To study the inhibitive effects of tumor angiogenesis by TTF1.METHODS Nude mice models were established by transplanting with human hepatocellular carcinoma HepG 2 cells,and 40 of nude mice models were divided into model group,apigenin group and small,middle and large dose（5,10,20 μmol/g） of TTF1 groups.After drug intervention for 21 days,nude mice models were sacrificed.CD34 expression was detected by immunohistochemistry,microvessel density（MD） was determined by Weidner capillary counting method,and the protein levels of vascular endothelial growth factor（VEGF）,KDR,basic fibroblast growth factor（bFGF）,hypoxia inducible factor-1 alpha（HIF-1α） and cyclooxygenase-2（COX-2） were detected by Western-blotting analysis.RESULTS The average MVD and the protein levels of VEGF,KDR,bFGF,HIF-1α and COX-2 in small,middle and large dose of TTF1 groups were significantly decreased.CONCLUSION TTF1 can inhibit tumor angiogenesis,and the mechanism may be associated with the down-regulation of VEGF,KDR,bFGF,HIF-1α and COX-2.