Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest

  • Authors:
    • Kiyoyuki Kobayashi
    • Asahiro Morishita
    • Hisakazu Iwama
    • Koji Fujita
    • Ryoichi Okura
    • Shintaro Fujihara
    • Takuma Yamashita
    • Takayuki Fujimori
    • Kiyohito Kato
    • Hideki Kamada
    • Toshiro Niki
    • Mitsuomi Hirashima
    • Keiichi Okano
    • Yasuyuki Suzuki
    • Tsutomu Masaki
  • View Affiliations

  • Published online on: August 10, 2015     https://doi.org/10.3892/or.2015.4197
  • Pages: 1761-1770
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Abstract

Cholangiocarcinoma is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC). Galectin-9 (Gal-9) is a tandem-repeat-type galectin that has recently been shown to exert antiproliferative effects on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human cholangiocarcinoma cells in vitro as well as the microRNAs (miRNAs) associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of cholangiocarcinoma cell lines in vitro and the growth of human cholangiocarcinoma cell xenografts in nude mice. Our data further revealed that Gal-9 increased caspase‑cleaved keratin 18 (CCK18) levels, and the expression of cytochrome c increased in Gal-9-treated cholangiocarcinoma cell lines. These data suggested that Gal-9 induced cholangiocarcinoma cell apoptosis via the intrinsic apoptosis pathway mediated by caspase-dependent or -independent pathways. In addition, Gal-9 reduced the phosphorylation of the epidermal growth factor receptor (EGFR), insulin-like growth factor and insulin-like growth factor-1 receptor (IGF-1R), hepatocyte growth factor receptor and fibroblast growth factor receptor 3 (FGFR3). These findings suggest that Gal-9 can be a candidate of therapeutic target in the treatment of cholangiocarcinoma.
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October-2015
Volume 34 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kobayashi K, Morishita A, Iwama H, Fujita K, Okura R, Fujihara S, Yamashita T, Fujimori T, Kato K, Kamada H, Kamada H, et al: Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest. Oncol Rep 34: 1761-1770, 2015
APA
Kobayashi, K., Morishita, A., Iwama, H., Fujita, K., Okura, R., Fujihara, S. ... Masaki, T. (2015). Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest. Oncology Reports, 34, 1761-1770. https://doi.org/10.3892/or.2015.4197
MLA
Kobayashi, K., Morishita, A., Iwama, H., Fujita, K., Okura, R., Fujihara, S., Yamashita, T., Fujimori, T., Kato, K., Kamada, H., Niki, T., Hirashima, M., Okano, K., Suzuki, Y., Masaki, T."Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest". Oncology Reports 34.4 (2015): 1761-1770.
Chicago
Kobayashi, K., Morishita, A., Iwama, H., Fujita, K., Okura, R., Fujihara, S., Yamashita, T., Fujimori, T., Kato, K., Kamada, H., Niki, T., Hirashima, M., Okano, K., Suzuki, Y., Masaki, T."Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest". Oncology Reports 34, no. 4 (2015): 1761-1770. https://doi.org/10.3892/or.2015.4197