Down-regulation of hypoxia-inducible factor-1 suppresses malignant biological behavior of triple-negative breast cancer cells

International Journal of Clinical and Experimental Medicine

Ling Hai¹  Yonghong Shi¹  Jing Zhao¹  Gaowa Sharen¹  Hua Du¹  Fang Wang¹  Miaomiao Chang¹  Lili Jiang¹ 

关键词: Hypoxia-inducible factor-1;    triple-negative breast cancer;    small-interfering RNA;    epithelial mesenchymal transition;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

This study is to investigate the effect and mechanism of reduced hypoxia-inducible factor (HIF)-1a expression on malignant behavior of MDA-MB-231 cells. HIF-1α expression was interfered by siRNA. Western blot was used to detect protein expression of HIF-1α, active fragments of caspase 3 and vimentin. Cell count, flow cytometry and Hoechst staining were used to evaluate cell growth and apoptosis. Matrigel invasion and wound scratch assay were performed to measure the ability of cell invasion and migration. After MDA-MB-231 cells were transfected with HIF-1α-targeted siRNA, HIF-1α protein expression was successfully interrupted and cell growth was retarded. Compared with random siRNA group, reduced HIF-1α protein expression in HIF-1α-targeted siRNA group facilitated cell apoptosis but had no effect on cell cycle. In addition, cells treated with HIF-1α-targeted siRNA expressed active fragments of caspase 3 (17 and 12 kD) after serum starvation for 0 to 60 h. Caspase 3 activity assay further confirmed the above finding. Reduced HIF-1α expression impaired the migration and invasiveness with a reduction in the expression of vimentin and CK18 protein. Inhibition of HIF-1α protein synthesis or enhancement of its degradation reversed its malignant phenotypes and could probably be a potential means for the treatment of triple-negative breast cancer.

【 授权许可】

Unknown