Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo

  • Authors:
    • Naoki Fujita
    • Koji Fujita
    • Hisakazu Iwama
    • Hideki Kobara
    • Shintaro Fujihara
    • Taiga Chiyo
    • Daisuke Namima
    • Hiroki Yamana
    • Toshiaki Kono
    • Kei Takuma
    • Masahiro Hirata
    • Kiyoyuki Kobayashi
    • Kiyohito Kato
    • Hideki Kamada
    • Asahiro Morishita
    • Kunihiko Tsutsui
    • Takashi Himoto
    • Keiichi Okano
    • Yasuyuki Suzuki
    • Tsutomu Masaki
  • View Affiliations

  • Published online on: May 7, 2020     https://doi.org/10.3892/or.2020.7607
  • Pages: 339-348
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Abstract

Gastric cancer is one of the most common malignancies diagnosed worldwide. Telmisartan, an angiotensin receptor blocker (ARB), suppresses the proliferation of cancer cells and the growth of tumors through an unknown mechanism. To identify the mechanism, the present study was designed to evaluate the effects of telmisartan on gastric cancer cell lines and tumors in vitro and in vivo and the associated signaling molecules were identified. It was shown here that telmisartan suppressed the proliferation of the cultured human gastric cancer cell lines MKN74, MKN1 and MKN45 as detected in the CCK‑8 assay. In a mouse xenograft model of gastric cancer, telmisartan suppressed tumor growth by arresting the cell cycle at the G0/G1 phase through inhibition of the expression of cyclin D1, the catalytic subunit of cyclin dependent kinase 4 (CDK4), as well as the phosphorylation of the tumor suppressor retinoblastoma (pRb) protein as detected by western blotting. Notably, telmisartan did not induce apoptosis, as indicated by consistent levels of caspase‑cleaved keratin 18 in MKN74 cells. Furthermore, telmisartan inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and increased the levels of the angiogenesis‑related protein tissue inhibitor of metalloproteinase‑1 (TIMP‑1). Analyses of microarrays revealed that telmisartan altered the expression of miRNAs in MKN74 cells. In conclusion, telmisartan suppressed the proliferation of human gastric cancer cells by inducing cell cycle arrest.

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July 2020
Volume 44 Issue 1

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

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APA
Fujita, N., Fujita, K., Iwama, H., Kobara, H., Fujihara, S., Chiyo, T. ... Masaki, T. (2020). Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo. Oncology Reports, 44, 339-348. https://doi.org/10.3892/or.2020.7607
MLA
Fujita, N., Fujita, K., Iwama, H., Kobara, H., Fujihara, S., Chiyo, T., Namima, D., Yamana, H., Kono, T., Takuma, K., Hirata, M., Kobayashi, K., Kato, K., Kamada, H., Morishita, A., Tsutsui, K., Himoto, T., Okano, K., Suzuki, Y., Masaki, T."Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo". Oncology Reports 44.1 (2020): 339-348.
Chicago
Fujita, N., Fujita, K., Iwama, H., Kobara, H., Fujihara, S., Chiyo, T., Namima, D., Yamana, H., Kono, T., Takuma, K., Hirata, M., Kobayashi, K., Kato, K., Kamada, H., Morishita, A., Tsutsui, K., Himoto, T., Okano, K., Suzuki, Y., Masaki, T."Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo". Oncology Reports 44, no. 1 (2020): 339-348. https://doi.org/10.3892/or.2020.7607