Proteasome Inhibitor Carfilzomib Enhances the Anticancer Effect of Paclitaxel in MDA-MB-231 Breast Cancer Cells
Medical Faculty, Department of Hematology, 1Department of Biochemistry, 2Faculty of Pharmacy, Department of Pharmacology, Faculty of Pharmacy, 3Medical Faculty, Department of Pharmacology, Sivas Cumhuriyet University, Sivas, Turkey
Medical Faculty, Department of Hematology, Sivas Cumhuriyet University, Sivas, Turkey, E-mail: [email protected]
This study was aimed to determine the anticancer efficacy of the combination of paclitaxel, the standard treatment of breast cancer, and carfilzomib, which is a proteasome inhibitor, in breast cancer cells in vitro. Paclitaxel, carfilzomib and their combinations at various concentrations were added to MDA-MB-231 human breast cancer cells, and cell viability was detected using the XTT assay. Combination index values were determined using the Chou-Talalay method. Apoptotic effect and cell cycle arrest of single administrations and combinations of these agents were also evaluated using the flow cytometry. According to the results of the XTT assay, the combination produced a greater anticancer effect than that produced by both agents administered alone. Chou-Talalay approaches exhibited that the combination of paclitaxel and carfilzomib demonstrated a synergistic effect. The flow analysis showed that the combinations have induced a cell cycle arrest of MDA-MB-231 cells at G2/M phase and significantly induced apoptosis. The present study revealed that carfilzomib could significantly increase the efficacy of paclitaxel in human breast cancer cells in vitro. It is recommended that carfilzomib to be used along with paclitaxel in metastatic breast cancer patients to increase the anticancer effect and reduce potential toxicity-related side effects.