Overcoming Hormone Resistance in Breast Cancer Cell Lines: The Impact of Combined Treatment with Sorafenib and Palbociclib on Cell Survival and Proliferation Pathways

The primary objective of this study was to investigate the potential synergy between Sorafenib, a multi-kinase inhibitor, and Palbociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, in the treatment of hormone receptor-positive breast cancer. Specifically, we aimed to determine whether the combination of these two drugs could enhance cell death in breast cancer cell lines. Methods: Cell Culture: Hormone receptor-positive breast cancer cell lines expressing estrogen receptors (ER-positive) and/or progesterone receptors (PR-positive) were selected for the study. Drug Treatment: Cells were treated with Sorafenib, Palbociclib, or a combination of both drugs. Cell Viability Assays: Cell viability and proliferation were assessed using MTT and BrdU assays, respectively. Immunoblotting: Protein expression and phosphorylation levels of key signaling molecules were analyzed to investigate the intracellular pathways affected by drug treatments. Statistical Analysis: Statistical comparisons were made between single-drug and combination-drug treatments to evaluate their effects on cell viability and proliferation. findings: Hormone receptor-positive breast cancer cells were chosen for this study due to their dependence on estrogen and progesterone for growth and division. Sorafenib, a multi-kinase inhibitor, effectively targeted multiple signaling pathways involved in cell proliferation, angiogenesis, and apoptosis, including Raf, VEGFR, PDGFR, and FLT3. Palbociclib, a CDK4/6 inhibitor, arrested cancer cells in the G1 phase of the cell cycle, preventing their progression into the S phase and subsequent proliferation. Contrary to expectations, the combination of Sorafenib and Palbociclib in hormone receptor-positive breast cancer cell lines did not result in enhanced cell death. Instead, it exhibited a proliferative effect. These unexpected results highlight the complexity of intracellular pathways and the potential for cross-talk between signaling pathways when drugs are combined.