FOXC2调控DLL4/Notch1信号通路对乳腺癌MCF-7细胞血管生成的影响

目的：探讨转录因子FOXC2对乳腺癌MCF-7细胞血管生成的影响，阐明FOXC2促进肿瘤血管生成的作用机制。方法：应用FOXC2慢病毒基因转染技术将FOXC2基因和空载体基因分别转染至乳腺癌MCF-7细胞株中，获得稳定转染细胞株；实验分为未转染组、空载体组和过表达组。采用Matrigel基质胶血管形成实验和Transwell小室实验检测各组细胞上清作用下人脐静脉内皮细胞（HUVECs）成管能力和迁移能力，RT-PCR和Western blotting法检测各组细胞中FOXC2、DLL4和Notch1 mRNA和蛋白表达。结果：与未转染组和空载体组比较，过表达组MCF-7细胞上清诱导HUVECs闭合小管数和迁移细胞数增加（P<0.05）；FOXC2、DLL4和Notch1 mRNA和蛋白相对表达水平明显增加（P<0.05）。结论：MCF-7细胞中过表达FOXC2能显著增加HUVECs的成管能力和迁移能力，其机制可能是通过Notch信号通路来实现的。

Influence of FOXC2 in angiogenesis of breast cancer MCF-7 cells by DLL4/Notch1 signal pathway

Objective To explore the influence of tranSCription factor FOXC2in angiogenesis of breast cancer MCF-7cells and to clarify the action mechanism of FOXC2in promoting tumor angiogenesis.Methods FOXC2 gene and empty vector gene were transfected into breast cancer of MCF-7cell line with FOXC2lentivirus gene transfection technique to obtain stable transfection cell line.The MCF-7cells were devided into non-transfected group,empty-vector group and over-expression group.Matrigel assay and Transwell chamber test were used to observe the changes of tube formation and migration ability of human umbilical vein endothelial cells(HUVECs)in MCF-7cells supernatant in various groups.PT-PCR and Western blotting methods were applied to detect the expressions of FOXC2,DLL4and Notch1mRNA and protein.Results Compared with non-tranfected group and empty-vector group,the tube formation and the migration number of HUVECs in FOXC2over-expression group were increased(P<0.05);the expressions of FOXC2,DLL4and Notch1mRNA and proteins were significantly increased(P<0.05).Conclusion The FOXC2over-expression in MCF-7cells can increase the tube formation ability and migration ability of HUVECs,and its mechanism may be related to Notch signaling pathway.