Open Access

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

  • Authors:
    • Huitao Xu
    • Ying Zhou
    • Wei Li
    • Bin Zhang
    • Huanhuan Zhang
    • Shaolin Zhao
    • Ping Zheng
    • Huiyi Wu
    • Jin Yang
  • View Affiliations

  • Published online on: April 11, 2018     https://doi.org/10.3892/ol.2018.8463
  • Pages: 9142-9150
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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June-2018
Volume 15 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Xu H, Zhou Y, Li W, Zhang B, Zhang H, Zhao S, Zheng P, Wu H and Yang J: Tumor‑derived mesenchymal‑stem‑cell‑secreted IL‑6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer. Oncol Lett 15: 9142-9150, 2018
APA
Xu, H., Zhou, Y., Li, W., Zhang, B., Zhang, H., Zhao, S. ... Yang, J. (2018). Tumor‑derived mesenchymal‑stem‑cell‑secreted IL‑6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer. Oncology Letters, 15, 9142-9150. https://doi.org/10.3892/ol.2018.8463
MLA
Xu, H., Zhou, Y., Li, W., Zhang, B., Zhang, H., Zhao, S., Zheng, P., Wu, H., Yang, J."Tumor‑derived mesenchymal‑stem‑cell‑secreted IL‑6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer". Oncology Letters 15.6 (2018): 9142-9150.
Chicago
Xu, H., Zhou, Y., Li, W., Zhang, B., Zhang, H., Zhao, S., Zheng, P., Wu, H., Yang, J."Tumor‑derived mesenchymal‑stem‑cell‑secreted IL‑6 enhances resistance to cisplatin via the STAT3 pathway in breast cancer". Oncology Letters 15, no. 6 (2018): 9142-9150. https://doi.org/10.3892/ol.2018.8463