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Article

Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer

  • Authors:
    • Takahisa Yamaguchi
    • Sachio Fushida
    • Yasuhiko Yamamoto
    • Tomoya Tsukada
    • Jun Kinoshita
    • Katsunobu Oyama
    • Tomoharu Miyashita
    • Hidehiro Tajima
    • Itasu Ninomiya
    • Seiichi Munesue
    • Ai Harashima
    • Shinichi Harada
    • Hiroshi Yamamoto
    • Tetsuo Ohta
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterologic Surgery, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8641, Japan, Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8641, Japan, Center for Biomedical Research and Education, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8641, Japan
  • Pages: 3341-3350
    |
    Published online on: April 19, 2017
       https://doi.org/10.3892/or.2017.5586
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Abstract

Tumor-associated macrophages of the M2 phenotype promote tumor proliferation and are associated with a poor prognosis in patients with various malignancies, including gastric cancer with peritoneal dissemination. The present study assessed whether paclitaxel (PTX) suppresses M2 macrophages, by acting as a Toll-like receptor 4 (TLR4) agonist. Macrophages derived from the THP-1 monocytic cell line and peripheral blood mononuclear cell (PBMC)-derived macrophages were cultured with gastric cancer cells in medium containing PTX, at a concentration that did not affect cell proliferation. The effects of PTX on macrophage expression of CD204, a marker of M2 macrophages and NOS2, a marker of M1 macrophages, was evaluated by western blotting. The ability of PTX to stimulate intranuclear translocation of NF-κB was determined by evaluating the expression of the p65 subunit of NF-κB. In THP-1 macrophages, low-dose PTX (1 and 5 nM) inhibited the expression of CD204, enhanced the expression of NOS2, and significantly suppressed the phosphorylation of Stat3, which is essential for the M2 phenotype. Low-dose PTX also inhibited CD204 expression in primary macrophages derived from PBMCs. PTX treatment of THP-1 macrophages for 1 h induced marked intranuclear translocation of NF-κB p65. Low-dose PTX inhibited the M2 phenotype and induced the M1 phenotype via TLR4 signaling, suggesting that low-dose PTX can alter the macrophage phenotype, whereas clinical doses can kill cancer cells. These results suggest that the anticancer effects of PTX are due both to its cytotoxic and immunomodulatory activities.
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Copy and paste a formatted citation
Spandidos Publications style
Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Tajima H, Ninomiya I, Munesue S, Munesue S, et al: Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer. Oncol Rep 37: 3341-3350, 2017.
APA
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K. ... Ohta, T. (2017). Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer. Oncology Reports, 37, 3341-3350. https://doi.org/10.3892/or.2017.5586
MLA
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., Harashima, A., Harada, S., Yamamoto, H., Ohta, T."Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer". Oncology Reports 37.6 (2017): 3341-3350.
Chicago
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., Harashima, A., Harada, S., Yamamoto, H., Ohta, T."Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer". Oncology Reports 37, no. 6 (2017): 3341-3350. https://doi.org/10.3892/or.2017.5586
Copy and paste a formatted citation
x
Spandidos Publications style
Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, Miyashita T, Tajima H, Ninomiya I, Munesue S, Munesue S, et al: Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer. Oncol Rep 37: 3341-3350, 2017.
APA
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K. ... Ohta, T. (2017). Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer. Oncology Reports, 37, 3341-3350. https://doi.org/10.3892/or.2017.5586
MLA
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., Harashima, A., Harada, S., Yamamoto, H., Ohta, T."Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer". Oncology Reports 37.6 (2017): 3341-3350.
Chicago
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., Harashima, A., Harada, S., Yamamoto, H., Ohta, T."Low-dose paclitaxel suppresses the induction of M2 macrophages in gastric cancer". Oncology Reports 37, no. 6 (2017): 3341-3350. https://doi.org/10.3892/or.2017.5586
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