Effects of MAPK pathway inhibitors (AZD6244) on resistance of breast cancer cells to chemotherapy and targeted therapy

Abstract

Advanced breast cancer is prone to metastasis, difficult to cure, and is characterized by frequent relapse following treatment. Chemotherapy and targeted therapy are the main treatments for patients with advanced breast cancer, but resistance to chemotherapy can affect outcomes and in severe cases lead to death. In recent years, the use of protein kinase inhibitors in tumor prevention and treatment has attracted considerable research interest. Exploring specific mechanisms of drug resistance to protein kinase inhibitors in breast cancer cells may help improve outcomes in breast cancer patients. In this study, the MAPK pathway inhibitor AZD6244 was applied to breast cancer cells and found to inhibit survival of the non-drug-resistant (NDR) cells MCF-7 and Ca151 more than the drug-resistant (DR) cells MCF-7/A02 and CALDOX. Activation of the MAPK/ERK pathway in DR breast cancer cells was found to be much greater than in NDR cells. In DR breast cancer cells, AZD6244 greatly reduced the activities of MAPK and ERK, and also the rate of proliferation, while increasing apoptosis. Therefore, these results are consistent with AZD6244 reducing proliferation and increasing apoptosis in DR breast cancer cells by inhibiting the MAPK/ERK pathway.