Open Access

Upregulation of integrin‑linked kinase enhances tumor progression in gemcitabine‑resistant pancreatic cancer

  • Authors:
    • Hiromichi Murase
    • Yoichi Matsuo
    • Yuki Denda
    • Keisuke Nonoyama
    • Tomokatsu Kato
    • Yoshinaga Aoyama
    • Yuichi Hayashi
    • Hiroyuki Imafuji
    • Kenta Saito
    • Mamoru Morimoto
    • Ryo Ogawa
    • Hiroki Takahashi
    • Akira Mitsui
    • Masahiro Kimura
    • Shuji Takiguchi
  • View Affiliations

  • Published online on: July 14, 2023     https://doi.org/10.3892/or.2023.8601
  • Article Number: 164
  • Copyright: © Murase et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic cancer (PaCa) tends to be resistant to chemotherapy and is associated with a very poor prognosis. It has been previously reported by the authors that integrin‑linked kinase (ILK) is a prognostic factor in PaCa. ILK expression was examined in a newly established gemcitabine (Gem)‑resistant (Gem‑R) PaCa cell line and it was demonstrated that ILK expression was upregulated compared with that in Gem‑sensitive (Gem‑S) cells. In the present study, the effects of increased ILK expression in Gem‑R PaCa cells were evaluated and it was examined whether compound 22 (Cpd22), an ILK inhibitor, exerted antitumor effects not only in Gem‑S cells but also in Gem‑R cells. Reverse transcription‑quantitative polymerase chain reaction and western blotting revealed that ILK expression was higher in Gem‑R PaCa cells than in Gem‑S PaCa cells. Cpd22 inhibited the growth of PaCa cells in a concentration‑dependent manner. Cpd22 also inhibited the growth of Gem‑R PaCa cells. The invasive and angiogenic potential of Gem‑R PaCa cells was enhanced compared with that in Gem‑S cells; however, ILK small interfering RNA and Cpd22 treatment suppressed this enhancement of invasive potential compared with that in Gem‑S cells. The addition of Cpd22 to Gem also improved the sensitivity of Gem‑R cell lines to Gem. Furthermore, enhanced Akt signaling was associated with increased malignancy in Gem‑R cell lines. In conclusion, ILK was upregulated with resistance and may be involved in tumor angiogenesis, invasive potential, and chemotherapy resistance, which were all suppressed by Cpd22 treatment. Thus, Cpd22 may be a novel therapeutic agent for the treatment of PaCa.
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September-2023
Volume 50 Issue 3

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

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Spandidos Publications style
Murase H, Matsuo Y, Denda Y, Nonoyama K, Kato T, Aoyama Y, Hayashi Y, Imafuji H, Saito K, Morimoto M, Morimoto M, et al: Upregulation of integrin‑linked kinase enhances tumor progression in gemcitabine‑resistant pancreatic cancer. Oncol Rep 50: 164, 2023
APA
Murase, H., Matsuo, Y., Denda, Y., Nonoyama, K., Kato, T., Aoyama, Y. ... Takiguchi, S. (2023). Upregulation of integrin‑linked kinase enhances tumor progression in gemcitabine‑resistant pancreatic cancer. Oncology Reports, 50, 164. https://doi.org/10.3892/or.2023.8601
MLA
Murase, H., Matsuo, Y., Denda, Y., Nonoyama, K., Kato, T., Aoyama, Y., Hayashi, Y., Imafuji, H., Saito, K., Morimoto, M., Ogawa, R., Takahashi, H., Mitsui, A., Kimura, M., Takiguchi, S."Upregulation of integrin‑linked kinase enhances tumor progression in gemcitabine‑resistant pancreatic cancer". Oncology Reports 50.3 (2023): 164.
Chicago
Murase, H., Matsuo, Y., Denda, Y., Nonoyama, K., Kato, T., Aoyama, Y., Hayashi, Y., Imafuji, H., Saito, K., Morimoto, M., Ogawa, R., Takahashi, H., Mitsui, A., Kimura, M., Takiguchi, S."Upregulation of integrin‑linked kinase enhances tumor progression in gemcitabine‑resistant pancreatic cancer". Oncology Reports 50, no. 3 (2023): 164. https://doi.org/10.3892/or.2023.8601