Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo

  • Authors:
    • Shintaro Fujihara
    • Kiyohito Kato
    • Asahiro Morishita
    • Hisakazu Iwama
    • Tomoko Nishioka
    • Taiga Chiyo
    • Noriko Nishiyama
    • Hisaaki Miyoshi
    • Mitsuyoshi Kobayashi
    • Hideki Kobara
    • Hirohito Mori
    • Keiichi Okano
    • Yasuyuki Suzuki
    • Tsutomu Masaki
  • View Affiliations

  • Published online on: February 24, 2015     https://doi.org/10.3892/ijo.2015.2903
  • Pages: 2172-2180
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Abstract

Esophageal carcinoma is the eighth most common cancer worldwide and the sixth leading cause of cancer-related deaths, with one of the worst prognoses of any form of cancer. Treatment with the anti-diabetic drug metformin has been associated with reduced cancer incidence in patients with type 2 diabetes. This study therefore evaluated the effects of metformin on the proliferation, in vitro and in vivo, of human esophageal adenocarcinoma cells, as well as the microRNAs associated with the antitumor effects of metformin. Metformin inhibited the proliferation of the esophageal adenocarcinoma cell lines OE19, OE33, SK-GT4 and OACM 5.1C, blocking the G0 to G1 transition in the cell cycle. This was accompanied by strong reductions in G1 cyclins, especially cyclin D1, cyclin-dependent kinase (Cdk)4, and Cdk6, and decreases in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of epidermal growth factor receptor and insulin-like growth factor and insulin-like growth factor-1 receptor, as well as angiogenesis-related proteins, such as vascular endothelial growth factor, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2. Metformin also markedly altered microRNA expression. Treatment with metformin of athymic nude mice bearing xenograft tumors reduced tumor proliferation. These findings suggest that metformin may have clinical use in the treatment of esophageal adenocarcinoma.
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May-2015
Volume 46 Issue 5

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

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Spandidos Publications style
Fujihara S, Kato K, Morishita A, Iwama H, Nishioka T, Chiyo T, Nishiyama N, Miyoshi H, Kobayashi M, Kobara H, Kobara H, et al: Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo. Int J Oncol 46: 2172-2180, 2015
APA
Fujihara, S., Kato, K., Morishita, A., Iwama, H., Nishioka, T., Chiyo, T. ... Masaki, T. (2015). Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo. International Journal of Oncology, 46, 2172-2180. https://doi.org/10.3892/ijo.2015.2903
MLA
Fujihara, S., Kato, K., Morishita, A., Iwama, H., Nishioka, T., Chiyo, T., Nishiyama, N., Miyoshi, H., Kobayashi, M., Kobara, H., Mori, H., Okano, K., Suzuki, Y., Masaki, T."Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo". International Journal of Oncology 46.5 (2015): 2172-2180.
Chicago
Fujihara, S., Kato, K., Morishita, A., Iwama, H., Nishioka, T., Chiyo, T., Nishiyama, N., Miyoshi, H., Kobayashi, M., Kobara, H., Mori, H., Okano, K., Suzuki, Y., Masaki, T."Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo". International Journal of Oncology 46, no. 5 (2015): 2172-2180. https://doi.org/10.3892/ijo.2015.2903