Ezetimibe suppresses the migration and invasion of triple-negative breast cancer cells by targeting TGFβ2 and EMT

Author:

He Qinyu1,Ma Ding1,Kong konglingkai1,Shi Weiwei1,Jiang Chunping1,Wu Junhua1,Xin Qilei2

Affiliation:

1. National Institute of Healthcare Data Science at Nanjing University, Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University

2. Jinan Microecological Biomedicine Shandong Laboratory, Shounuo City Light West Block, Qingdao Road 3716#, Huaiyin District, Jinan City, Shandong Province, China.

Abstract

Abstract In recent years, the important role of cholesterol in tumor metastasis has been revealed. Ezetimibe is the only selective cholesterol uptake inhibitor currently on the market. Here, we aimed to explore the effect of ezetimibe on breast cancer metastasis. The effects of ezetimibe on breast cancer cell migration, invasion, and EMT were examined by wound healing assay, invasion assay, and western blotting assay. After ezetimibe treatment of breast cancer cells, differentially expressed genes were investigated by transcriptome sequencing and validated by western blotting assay and qRT-PCR. Breast cancer cells overexpressing TGFβ2 were constructed, and the effect of TGFβ2 on the migration and invasion of ezetimibe-treated breast cancer cells was examined by wound healing and invasion assays. The study showed that ezetimibe inhibited the migration, invasion, and EMT of breast cancer cells and significantly suppressed the expression of TGFβ2 in breast cancer cells. Enhanced TGFβ2 expression reversed the inhibitory effect of ezetimibe on the migration and invasion of breast cancer cells. This study demonstrates that ezetimibe is a potential drug for the treatment of breast cancer metastasis.

Publisher

Research Square Platform LLC

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