Open Access

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

  • Authors:
    • Eri Samukawa
    • Shintaro Fujihara
    • Kyoko Oura
    • Hisakazu Iwama
    • Yoshimi Yamana
    • Tomoko Tadokoro
    • Taiga Chiyo
    • Kiyoyuki Kobayashi
    • Asahiro Morishita
    • Mai Nakahara
    • Hideki Kobara
    • Hirohito Mori
    • Keiichi Okano
    • Yasuyuki Suzuki
    • Takashi Himoto
    • Tsutomu Masaki
  • View Affiliations

  • Published online on: October 23, 2017     https://doi.org/10.3892/ijo.2017.4177
  • Pages:1674-1684
  • Copyright: © Samukawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cholangiocarcinoma (CCA) is at an advanced stage at the time of its diagnosis, and developing a more effective treatment of CCA would be desirable. Angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan may inhibit cancer cell proliferation, but the mechanisms by which telmisartan affects various cancers remain unknown. In this study, we evaluated the effects of telmisartan on human CCA cells and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on CCA cells using two cell lines, HuCCT-1 and TFK-1. In our experiments, telmisartan inhibited the proliferation of HuCCT-1 and TFK-1 cells. Additionally, telmisartan induced G0/G1 cell cycle arrest via blockade of the G0 to G1 cell cycle transition. Notably, telmisartan did not induce apoptosis in HuCCT-1 cells. This blockade was accompanied by a strong decrease in cell cycle-related protein, especially G1 cyclin, cyclin D1, and its catalytic subumits, Cdk4 and Cdk6. Telmisartan reduced the phosphorylation of EGFR (p-EGFR) and TIMP-1 by using p-RTK and angiogenesis array. Furthermore, miRNA expression was markedly altered by telmisartan in HuCCT-1. Telmisartan inhibits tumor growth in CCA xenograft model in vivo. In conclusion, telmisartan was shown to inhibit human CCA cell proliferation by inducing cell cycle arrest.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
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APA
Samukawa, E., Fujihara, S., Oura, K., Iwama, H., Yamana, Y., Tadokoro, T. ... Masaki, T. (2017). Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest. International Journal of Oncology, 51, 1674-1684. https://doi.org/10.3892/ijo.2017.4177
MLA
Samukawa, E., Fujihara, S., Oura, K., Iwama, H., Yamana, Y., Tadokoro, T., Chiyo, T., Kobayashi, K., Morishita, A., Nakahara, M., Kobara, H., Mori, H., Okano, K., Suzuki, Y., Himoto, T., Masaki, T."Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest". International Journal of Oncology 51.6 (2017): 1674-1684.
Chicago
Samukawa, E., Fujihara, S., Oura, K., Iwama, H., Yamana, Y., Tadokoro, T., Chiyo, T., Kobayashi, K., Morishita, A., Nakahara, M., Kobara, H., Mori, H., Okano, K., Suzuki, Y., Himoto, T., Masaki, T."Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest". International Journal of Oncology 51, no. 6 (2017): 1674-1684. https://doi.org/10.3892/ijo.2017.4177