Chemotherapeutic Effect of Stigmasterol in Sorafenib Treated Breast Cancer Cell Lines via Modulation of NF-B and ERK Signaling Pathways

Breast cancer is the main predisposing factor for female tumor -related death globally, which increases the requirement to investigate the effectiveness of new drug combination strategies. Sorafenib is a multi-kinase inhibitor mainly targeting vascular endothelial growth factor receptor (VEGFR) and Ras/Raf/ Extracellular signal -regulated kinase (ERK) pathway. Stigmasterol is a phytosterol with anticancer activity targeting different oncogenic pathways. This study aimed to examine the antitumor effects of stigmasterol and sorafenib combination against MDA-MB-231 and MCF-7 breast cancer cell lines via assessing their impact on VEGF, VEGFR-2, nuclear factor kappa B (NF-kappa B), Ki-67, Bcl-2, ERK, and caspase-3. Cytotoxicity was investigated using the MTT assay. VEGF, VEGFR-2, ERK, NF-kappa B, Bcl-2, and Ki-67 levels were assessed using the ELISA technique. VEGFR-2 gene expression was assessed using the RT-PCR technique, while caspase-3 activity was investigated using the colorimetric technique. Sorafenib and stigmasterol combination reduced the levels of NF-kappa B, Bcl-2, Ki- 67, VEGFR-2, and VEGF-A, whereas the activity of caspase-3 was increased. Stigmasterol and sorafenib combination may be a promising therapeutic regimen for breast cancer treatment through modulation of NF-kappa B-VEGF/BCL-2 and ERK/Caspase-3 signaling axes crosstalk.