Overcoming Hormone Resistance in Breast Cancer Cell Lines: The Impact of Combined Treatment with Sorafenib and Palbociclib on Cell Survival and Proliferation Pathways
Elvina Almuradova1, Erkan Kahraman2, Erdem Goker31Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Türkiye Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Türkiye, 2Ege University, Research and Application Center of Individualized Medicine, Izmir, Türkiye, 3Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Türkiye
Objectives: 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. Results: Our study revealed the following key 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. Conclusion: In conclusion, our study emphasizes the intricate and multifaceted nature of intracellular pathways in hormone receptor-positive breast cancer. The unanticipated proliferative effect of the Sorafenib and Palbociclib combination underscores the importance of considering all possible mechanisms of action when designing drug combinations for cancer treatment. This study serves as a valuable reminder that therapies should not solely depend on the modulation of a single pathway but rather take into account the intricate web of interactions within the cellular environment. Further research is warranted to elucidate the underlying molecular mechanisms responsible for the observed outcomes and to guide the development of more effective treatment strategies for hormone receptor-positive breast cancer. Keywords: Breast cancer, Cyclin-Dependent Kinase, mitogen-activated protein kinase
Cite This Article
Almuradova E, Kahraman E, Goker E. Overcoming Hormone Resistance in Breast Cancer Cell Lines: The Impact of Combined Treatment with Sorafenib and Palbociclib on Cell Survival and Proliferation Pathways. EJMI. 2024; 8(1): 13-20
Corresponding Author: Elvina Almuradova