Background: Breast cancer is the most common invasive malignancy and the leading cause of tumor-related death among women globally. Excessive angiogenesis, sustained proliferation, and evasion of apoptosis are crucial for breast cancer progression. Sorafenib is a multi-kinase receptor inhibitor with anti-angiogenic activity. Stigmasterol is a phytosterol with anticancer activity. The aim of this study was to investigate molecular mechanisms of action of sorafenib and stigmasterol in two

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... t human breast cancer cell lines and assess their combined impact on modulation of signaling pathways that control breast cancer pathogenesis. Methods and results: MCF-7 and MDA-MB 231 cells were used as models of human breast cancer. MTT assay was used to assess cytotoxicity. Angiogenic VEGF/ VEGFR-2/ ERK/ NF-kB signaling pathway was investigated using ELISA and RT-PCR techniques. Apoptotic markers (caspase-3, Bcl2) and a proliferation marker (Ki-67) were assessed using colorimetric and ELISA techniques. Sorafenib combined with stigmasterol increased caspase-3 activity and decreased Bcl2, VEGF-A, VEGFR-2, NF-kB and Ki-67 levels. Conclusion: The combination of Sorafenib and stigmasterol may be a useful therapeutic regimen for breast cancer treatment. This combination may inhibit angiogenesis and promote apoptosis signaling.