Enhanced Antiproliferation Potency of Electrical Pulse-Mediated Metformin and Cisplatin Combination Therapy on MDA-MB-231 Cells.

Abstract

We investigated the combined potency of metformin and cisplatin on the MDA-MB-231, triple-negative breast cancer (TNBC) cells with the application of electrical pulses. There are no targeted therapies for this subset of breast cancer because of the absence of specific biomarkers. Cytotoxic chemotherapy is the mainstream mode of treatment for TNBC, and cisplatin is the most commonly used chemotherapeutic drug. While there is a good response initially, TNBC cells develop drug resistance eventually. Thus, there is a need for alternate therapies. Toward this, we studied the antiproliferation characteristics of electrical pulse-mediated combination therapy using metformin, the commonly used Type-2 diabetes drug, along with cisplatin. We used metformin, as it has various anticancer properties caused by repressing energy pathways in a cancer cell. Application of 8 pulses of 1000V/cm, 100µs, at 1Hz frequency, enhanced the drug uptake leading to cell viability as low as 25.86% at 30µM cisplatin and 5mM metformin in a 24h study. Also, the same studies were conducted on MCF10A, a non-cancerous human epithelial cell. It aided in comparing the result for both MDA-MB-231 and MCF10A cell lines while establishing a better understanding of the experimental outcomes. Overall, the various experimental results from colony-forming assay, reactive oxidative analysis, and the intracellular glucose metabolic assay indicate the possibility of the electrical pulses-based cisplatin and metformin drug combination as a potential alternative to TNBC treatment.