Raloxifene potentiates the effect of gefitinib in triple-negative breast cancer cell lines.
Sebastien TaurinRhonda J RosengrenPublished in: Medical oncology (Northwood, London, England) (2022)
Triple-negative breast cancers (TNBCs) are characterized by a lack of approved targeted therapies and remain a challenge in the clinic. Several overexpressed proteins, including epidermal growth factor receptor (EGFR), have been associated with TNBCs and are considered potential therapeutic targets. However, EGFR inhibitors alone failed to demonstrate a cutting-edge advantage for treating TNBCs over conventional chemotherapies. Studies have shown that selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene also affect TNBC cell viability. The combination of gefitinib and raloxifene was assessed against TNBC cell lines in vitro. Two TNBC cell lines, MDA-MB-231 and MDA-MB-468, were used to investigate the combination of gefitinib and raloxifene on cell viability, DNA synthesis, and apoptosis. The combination was assessed on intracellular signaling pathways, colony formation, migration, and angiogenesis. In the present study, raloxifene, in combination with gefitinib, decreased cell viability. The combination potentiates apoptosis and affects the expression and phosphorylation pattern of proteins involved in cell proliferation, such as NFκB, β-catenin, and EGFR. Furthermore, evidence of apoptosis activation was also observed, along with a decreased cell migration and tumorigenicity of TNBC cells. Moreover, the combined treatment decreased the ability of neovascularization as assessed by tube formation of endothelial cells. These results suggested the potential of the combination of raloxifene and gefitinib for the prevention of TNBC growth and the appearance of metastatic events. Our findings provide the basis for future studies on the mechanism involved in raloxifene-gefitinib inhibition of ER-negative tumor growth.
Keyphrases
- epidermal growth factor receptor
- small cell lung cancer
- cell cycle arrest
- tyrosine kinase
- advanced non small cell lung cancer
- estrogen receptor
- pi k akt
- cell proliferation
- endothelial cells
- cell death
- oxidative stress
- endoplasmic reticulum stress
- signaling pathway
- breast cancer cells
- induced apoptosis
- cell migration
- squamous cell carcinoma
- epithelial mesenchymal transition
- immune response
- lps induced
- inflammatory response
- risk assessment
- human health
- climate change
- diabetic retinopathy
- circulating tumor
- toll like receptor
- positive breast cancer