Functional combination of resveratrol and tamoxifen to overcome tamoxifen‐resistance in breast cancer cells

Abstract Researchers are encountering challenges in addressing the issue of cancer cells becoming unresponsive to various chemotherapy treatments due to drug resistance. This study was designed to study the influence of antioxidant resveratrol (RSV) to sensitize resistant breast cancer (BC) cells toward tamoxifen (TAM). The cytotoxic effects of RSV and TAM against TAM‐resistant LCC2 cells and their parental michigan cancer foundation‐7 BC cells were determined by sulphorhodamine B assay. Further, the expression levels of multidrug resistance (MDR) genes including ABCB1 , ABCC2 , ABCG2 , and MRP1 using quantitative polymerase chain reaction, apoptosis induction, and reactive oxygen species (ROS) content using flow cytometry were evaluated in either LCC2 cells treated with RSV, TAM, or their combination. The obtained results showed that resistant cells have a magnificent level of MDR genes. This elevated expression dramatically lowered upon receiving the combined therapy of RSV and TAM. Additionally, our work assessed the possible role of RSV in modulating the expression of MDR genes by controlling the expression of certain microRNAs (miRNAs) that target ATP‐binding cassette (ABC) transporters. According to the obtained data, the TAM and RSV combination increased the expression of tumor inhibitor miRNAs such miR‐10b‐3p, miR‐195‐3p, and miR‐223‐3p, which made LCC2 cells more sensitive to TAM. Furthermore, this combination showed an elevation in apoptotic levels and total ROS content. The combination between RSV and TAM could be a functional therapy in the fight against TAM‐resistant BC cells via modulating miRNA and ABC transporters.