Resveratrol chemosensitizes adriamycin-resistant breast cancer cells by modulating miR-122-5p.

Abstract

Breast cancer is one of the major malignancies threatening women's health worldwide, and chemotherapy tolerance has become a severe limitation of clinical treatment. Recent findings have revealed that resveratrol, as a dietary agent with antitumour activity, could prevent cancer progression by regulating microRNAs (miRNAs). Additionally, dysregulated miRNAs have been found to contribute significantly to chemoresistance by an increasing number of studies. In this study, experiments were designed to study the functional role of resveratrol in MCF-7 cells (low-invasive breast cancer) in chemosensitivity to adriamycin and to determine the targeted miRNAs of resveratrol and their key target proteins linked to cell activity. We demonstrated that in resveratrol-induced chemosensitivity, cell cycle and apoptosis were arrested in adriamycin-resistant breast cancer cells after modulation of the critical suppresser, miR-122-5p. Further miRNA modulation with miR-122-5p mimics or miR-122-5p inhibitors indicated a major effect of miR-122-5p on the regulation of key antiapoptotic proteins (B-cell lymphoma 2 [Bcl-2]) and cyclin-dependent kinases (CDK2, CDK4, and CDK6) in drug-resistant breast cancer cells in response to resveratrol. In conclusion, our results indicate that resveratrol acts as a potential inducer to enhance the chemosensitivity of breast cancer and also suggest that miR-122-5p is involved in the pathway of cell-cycle arrest by targeting Bcl-2 and CDKs.