Knocking down HIF-1α expression inhibits lung metastasis of breast cancer cell line 4T1 by attenuating EMT

Abstract Background: Globally, women’s healthy and survival were threatened by breast cancer. Clarify the mechanism of distal metastasis of breast cancer will provide precise control and prolong patients’ lifetime. It’s well known that HIF-1α play important roles in breast cancer, however, few studies have directly examined the impact of knocking down HIF-1α on lung metastasis of breast cancer. In this study, HIF-1α was knocked down in mice breast cancer cell line 4T1 to explore its role on breast cancer lung metastasis.Methods: HIF-1Α knocked down lentivirus pHBL-U6-MSC-shHIF-1Α-GFP-PURO was transfected to 4T1 cells to construct HIF-1α low expression cells model while pHBL-U6-MSC-GFP-PURO was used as control. The transfection efficiency of lentivirus was observed by fluorescence microscope and flow cytometry, HIF-1α knock down was tested by Q-PCR and western blot. Would healing and transwell migration were used to detect the migration ability of cells in vitro. Mouse lung metastasis model was used to verify cells metastasis in vivo.Results: Lower expression of HIF-1α was detected in HIF-1Α knocked down 4T1 cells. Decreased HIF-1α expression repressed migration of 4T1 cells in vitro and reduced lung metastasis in mice breast cancer model. Moreover, HIF-1α’s down expression sponges E-cadherin up-regulation and Vimentin down-regulation to inhibit EMT, therefor reduced lung metastasis.Conclusions: our study revealed that HIF-1α knocked down inhibited lung metastasis of 4T1 breast cancer in vivo by suppressed EMT, thus inspiring a new treatment for breast cancer.