The investigation of the synergetic and cytotoxic effects of the doxorubicin and omeprazole on the MCF-7 cancer cell line

Breast cancer is the most common type of malignant disease among woman worldwide. In developing countries, the incidence of this type of cancer has increased in the last few years. Today, breast cancer is second leading cause of cancer-related deaths. Since the current treatment methods used in cancer treatment bring side effects, new treatment methods are needed. For this purpose, the combined use of two or more drugs is an effective way of cancer treatment. In this study, doxorubicin and omeprazole were administered singly and in combination on MCF-7 cells in a dose and time dependent manner. Combined use aims to increase the therapeutic effec and reduce the resistance to chemotherapeutic agents and side effects. Doxorubicin, an anthracycline antibiotic, is an anticancer agent widely used in many cancers to induce tumor cell apoptosis. Omeprazole is a gastric proton pump inhibitor. MCF-7 is a cell line commonly used in breast cancer studies. The aim of this study was to investigate the cytotoxic and synergetic activities of the anticancer agent doxorubicin and the proton pump inhibitor omeprazole on MCF-7 cells, separately and in combination. In addition, this study was designed to investigate whether a proton pump inhibitor could increase the efficacy of a cytotoxic agent used in breast cancer. For this reason, IC50 doses were determined by MTT assay as a result of single and combined administration of the active substances. Then, the synergetic effect was calculated and RNA isolation and cDNA synthesis assay for qPCR experiments were performed. The effects of active substances on apoptosis were determined by flow cytometry. It was determined in which pathway the mRNAs that showed significant chanes in the results of qPCR experiments on MCF-7 cell line using doxorubicin and omeprazole seperately and in combination were involved. The effects of proton pump inhibitor, which causes apoptotic effect in MCF-7 breast cancer cell line, were shown at gene expression level expression in signallingg pathways. As a result, it was shown that the anticancer efficacy of doxorubicin increased with proton pump inhibitor. Combined administration showed a stronger cytotoxic effect on cells than single administration.