Evaluation of cisplatin and carfilzomib, alone and in combination, on intracellular pNF-κB p65 levels in an ovarian cancer cell line

Background: Ovarian cancer remains one of the leading causes of cancer-related mortality among women, with chemoresistance presenting a significant challenge to effective treatment.Objectives: The aim of this study is to evaluate the cytotoxic effects of cisplatin (Cis) and carfilzomib (CFZ), both individually and in combination, and to assess their impact on intracellular levels of phosphorylated NF-κB p65 (pNF-κB p65) in Cis -sensitive (A2780S) and Cis-resistant (A2780CisR) ovarian cancer cell lines.Methods: in this experimental study, A2780S and A2780CisR cells were treated with varying concentrations of Cis, CFZ, and their combination. Cell viability was assessed using the MTT assay to determine the IC50 values, and drug interactions were analyzed using CompuSyn software. Additionally, intracellular pNF-κB p65 levels were quantified using an enzyme-linked immunosorbent assay (ELISA).Results: The A2780CisR cells demonstrated significant resistance to Cis; however, CFZ effectively inhibited cell proliferation in both cell lines. Notably, the combination of Cis and CFZ exhibited a synergistic effect, particularly pronounced in A2780S cells. Treatment with CFZ resulted in a significant reduction in pNF-κB p65 levels across both cell lines, indicating that CFZ may help overcome Cis resistance by targeting the NF-κB pathway.Conclusion: CFZ shows promise as a therapeutic strategy to enhance Cis sensitivity in ovarian cancer through modulation of the NF-κB signaling pathway. These findings provide a potential new approach for overcoming chemoresistance and improving patient outcomes.