Tumor-derived mesenchymal-stem-cell-secreted IL-6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer

Abstract

Cisplatin is used for the treatment of a range of solid malignant tumors; however, with prolonged treatment durations, the sensitivity of tumor cells to the drug decreases owing to an unclear mechanism of drug resistance. The present study aimed to investigate whether breast-cancer-tissue-derived mesenchymal stem cells (BC-MSCs) are involved in mediating the effects of cisplatin on breast cancer cells, and which component of the BC-MSC conditioned medium (BC-MSC-CM) exhibited an anti-apoptotic effect. Cytokines/chemokines in BC-MSC-CM were quantified using a Luminex immunoassay, and reverse transcription-quantitative polymerase chain reaction analysis detected interleukin-6 (IL-6) levels in MCF-7 cells following different treatments. MTT and flow cytometry analysis measured cell vitality and apoptosis, respectively, and activation of signal transduced and activator of transcription 3 (STAT3) was evaluated by western blotting. BC-MSCs reversed the pro-apoptotic effect of cisplatin and enhanced the proliferation of MCF-7 cells more potently than bone-marrow-derived MSCs. Further study revealed that BC-MSCs secreted IL-6 to protect MCF-7 cells from apoptosis and promote their survival. Neutralizing IL-6 with a specific antibody partially inhibited the IL-6/STAT3 signaling pathway and reversed the promoter role of BC-MSCs in MCF-7 cells. Taken together, the findings of the present study indicated that BC-MSCs decreased the level of cisplatin-induced apoptosis in MCF-7 cells by activating the IL-6/STAT3 pathway in cancer cells. BC-MSCs, as important cells in the tumor microenvironment, have a key role in the treatment of breast cancer.