HIF-1α对乳腺癌MCF-7细胞裸鼠血行肺转移能力的影响及机制

Effects of HIF-1α on the metastatic ability of human breast cancer cell line MCF-7 (study of animal model)

目的:干扰HIF-1α表达,建立乳腺癌血行转移的动物模型,检验HIF-1α表达在血行肺转移中的作用。方法:慢病毒转染干扰乳腺癌细胞系MCF-7中HIF-1α的表达,得到HIF-1α表达正常的乳腺癌细胞系MCF-7-NC和HIF-1α表达受干扰的细胞系MCF-7-HIF。分别将两组细胞系进行裸鼠鼠尾静脉注射建立乳腺癌血行转移模型,检测两组细胞在小鼠肺部形成转移瘤的能力。免疫组化方法检测2组肺转移灶中E-钙黏素和Notch-1受体胞内结构域(Notch-1 intracellular domain,NICD)的表达情况。结果:注射MCF-7-NC组裸鼠肺部转移瘤数量、大小均高MCF-7-HIF组,MCF-7-NC组平均成瘤数22.4±4.1个,MCF-7-HIF组13.8±3.2个。肺最大转移瘤平均直径MCF-7-NC组3.2mm,MCF-7-HIF组2.5mm。胸水的出现,MCF-7-NC组显著高于MCF-7-HIF组。免疫组化结果提示MCF-7-NC组E-钙黏素低表达,NICD高表达,而MCF-7-HIF组恰好与其相反。结论:干扰HIF-1α的表达,可以显著减低乳腺癌细胞系MFC-7的血行肺转移能力。转移灶中E-钙黏素和NICD的表达与HIF-1α表达是否受干扰密切相关。

Objective：To study the effects of HIF -1α on the metastatic ability of breast cancer cell line MCF - 7. Through the breast cancer blood metastasis modal in nude mice,we tested the important role of HIF -1α in the process of blood metastasis. Metbods：Lentivirus infections were carried on to obtain the MCF -7 - NC whose expression of HIF -1α was normal, and MCF - 7 - HIF that expression of HIF - 1α was interfered, in nude mice exenografts ,we injected same quantity of normal breast cancer cells and HIF -1α expression was interfered through vena caudalis. The pulmonary metastasis foci were evaluated to demonstrate HIF - 1α expression effect on the metastasis ability of breast cancer cell. hmnunohistochemical analysis was used to detect the expression of E - cadherin and NICD in pulmonary metastasis foci to detect the effect of HIF - 1α on the EMT of breast cancer cell and the activation of Notch - 1 pathway. Results：in nude mice exenografts,there were 13 of 14 mice arisen pulmonary metastasis in the group injected MCF - 7 - NC, versus 9 of 13 mice in MCF - 7 - HIF group, in MCF - 7 - NC group, there were 3 mice with the clinical symptom hydrothorax,versus none in the other group. The average number of metastasis loci per mouse in MCF - 7 - NC group was 22.4 ± 4.1 ,versus 13.8 ± 3.2 in the other group. The average diameter of the maximum foci was 3.2mm in MCF - 7 - NC group versus 2.5mm. MCF - 7 - NC group was remarkably superior to the MCF -7 - HIF group in metastasis rate, number of metastasis and volume of metastasis sults showed low expression of E - cadherin and high expression of NICD in MCF -7 - NC group versus high expression of E - eadherin and low expression of NICD in other group. Concluslon：Nude mice exenografts concluded the interference of HIF - 1α expression conspicuously lead to the decline of the metastasis ability of breast cancer cell line MCF -7.