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2018 ; 15
(6
): 9142-9150
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Tumor-derived mesenchymal-stem-cell-secreted IL-6 enhances resistance to
cisplatin via the STAT3 pathway in breast cancer
#MMPMID29844821
Xu H
; Zhou Y
; Li W
; Zhang B
; Zhang H
; Zhao S
; Zheng P
; Wu H
; Yang J
Oncol Lett
2018[Jun]; 15
(6
): 9142-9150
PMID29844821
show ga
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.
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