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Article

Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner

  • Authors:
    • Qiang Liu
    • Lei Dong
    • Hong Li
    • Jia Yuan
    • Yuping Peng
    • Shejiao Dai
  • View Affiliations / Copyright

    Affiliations: Department of Radiology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
  • Pages: 315-323
    |
    Published online on: April 26, 2016
       https://doi.org/10.3892/or.2016.4769
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Abstract

Bone marrow (BM) suppression (also known as myelosuppression) is the most common and most severe side-effect of therarubicin (THP) and thereby limits the clinical application of this anticancer agent. Lentinan (LNT), a glucan extracted from dried shiitake mushrooms (Lentinula edodes), exhibits a variety of pharmacological activities. The objectives of the present study were to determine the effect of LNT on the myelosuppression of THP-treated mice and to examine the pharmacological mechanism of these effects. In vivo experiments indicated that non-cytotoxic levels of LNT strongly increased blood myeloperoxidase (MPO) activity; improved BM structural injuries; increased the numbers of leukocytes and neutrophils in the blood and BM; elevated the blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF); and reduced the self-healing period in THP-treated mice. In vitro experiments indicated that LNT increased the viability of BM-derived macrophages (BMDMs) in a time- and dose-dependent manner without toxic side-effects and markedly increased the release of G-CSF, GM-CSF and M-CSF by BMDMs. Further analyses revealed that LNT activated the NF-κB and MAPK signalling pathways and promoted the nuclear import of p65 and that BAY 11-7082 (a specific inhibitor of NF-κB) suppressed the release of G-CSF, GM-CSF and M-CSF. Furthermore, we found that U0126, SB203580 and SP600125 (specific inhibitors of ERK, p38 and JNK, respectively) markedly inhibited the IKK/IκB/NF-κB-dependent release of G-CSF, GM-CSF and M-CSF. In conclusion, LNT induces the production of G-CSF, GM-CSF and M-CSF by activating the MAPK/NF-κB signalling pathway in BM cells, thereby mitigating THP-induced myelosuppression.
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Copy and paste a formatted citation
Spandidos Publications style
Liu Q, Dong L, Li H, Yuan J, Peng Y and Dai S: Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner. Oncol Rep 36: 315-323, 2016.
APA
Liu, Q., Dong, L., Li, H., Yuan, J., Peng, Y., & Dai, S. (2016). Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner. Oncology Reports, 36, 315-323. https://doi.org/10.3892/or.2016.4769
MLA
Liu, Q., Dong, L., Li, H., Yuan, J., Peng, Y., Dai, S."Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner". Oncology Reports 36.1 (2016): 315-323.
Chicago
Liu, Q., Dong, L., Li, H., Yuan, J., Peng, Y., Dai, S."Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner". Oncology Reports 36, no. 1 (2016): 315-323. https://doi.org/10.3892/or.2016.4769
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Q, Dong L, Li H, Yuan J, Peng Y and Dai S: Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner. Oncol Rep 36: 315-323, 2016.
APA
Liu, Q., Dong, L., Li, H., Yuan, J., Peng, Y., & Dai, S. (2016). Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner. Oncology Reports, 36, 315-323. https://doi.org/10.3892/or.2016.4769
MLA
Liu, Q., Dong, L., Li, H., Yuan, J., Peng, Y., Dai, S."Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner". Oncology Reports 36.1 (2016): 315-323.
Chicago
Liu, Q., Dong, L., Li, H., Yuan, J., Peng, Y., Dai, S."Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner". Oncology Reports 36, no. 1 (2016): 315-323. https://doi.org/10.3892/or.2016.4769
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