Anticancer activity of methotrexate in electrochemotherapy and electrochemotherapy plus ionizing radiation treatments in human breast cancer cells

Abstract

Traditional cancer treatments, such as chemotherapy and radiotherapy have several limitations. Therefore, their performance must be enhanced with combined methods. The purpose of this study is to investigate both the efficacy of electroporation (EP) on the activity of methotrexate (MTX) and the combined treatment of electrochemotherapy (ECT) + ionizing radiation (IR) in MCF-7 cancer cells. Different treatment techniques, such as EP, MTX, MTX + EP (ECT), 140 kV X-ray alone (IR_140kV), 500 kV X-ray alone (IR_500kV), ECT + IR_140kV and ECT + IR_500kV, were applied to cancer cells. Eight electric pulse trains with square wave (800 V/cm, 100 µs and 1 Hz) were used in EP and ECT applications. The MTT assay was used to assess the efficacy of the therapies used. When the EP, MTX, ECT, IR_140kV, and IR_500kV treatment groups were compared to the control group, there was a significant reduction in MCF-7 cancer cells viability (p < 0.05). ECT was the most effective of these treatments, decreasing viability of cancer cells to 58.78%. The ECT + IR_140kV and ECT + IR_500kV groups were compared to the ECT group to examine the impact of X-ray radiation on ECT treatment. When compared to the ECT alone group, both groups that exposed to X-rays after ECT had a significant decrease in cell viability (p < 0.05). Furthermore, viability of MCF-7 cells reduced to 46.38% in the ECT + IR_140kV group and 35.89% in the ECT + IR_500kV group. In conclusion, the study shows that the cytotoxicity of MTX is significantly increased in ECT treatment compared to standard chemotherapy (p < 0.05). In addition, ECT + IR combined therapy application is much more effective than MTX or ECT treatments alone. Graphical Abstract: [Figure not available: see fulltext.]. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.