Sorafenib Inhibits Proliferation, Migration and Invasion of Breast Cancer Cells.

INTRODUCTION: Metastatic breast cancer has poor prognosis due to limited therapeutic options. Protein kinase dysregulations have a major role in breast cancer progression and metastasis. In this study, we investigated the anti-cancer activity of sorafenib, a multikinase inhibitor, which targets receptor tyrosine kinases in breast cancer. Although treatment with sorafenib has increased the patient survival and inhibited metastatic migration in hepatocellular carcinoma, its role in breast cancer migration, metastasis, and intracellular signaling modulation is unknown. METHODS: Breast cancer cell lines MCF7 and MDA-MB-231 were treated with sorafenib and its effect on proliferation, migration, invasion and gene expression was analyzed. RESULTS: We found that sorafenib has an anti-proliferative and cytotoxic effect on breast cancer cells. Importantly, sorafenib inhibited the migration and invasion of breast cancer cells in vitro. Mechanistically, sorafenib increased mitochondrial superoxide production, suppressed breast cancer stem cell self-renewal, inhibited epithelial mesenchymal transition and ERK signaling. CONCLUSION: Thus, sorafenib has anti-cancer activity against breast cancer cells and could improve the survival of breast cancer patients by inhibiting their invasive and metastatic properties.