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Article

Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1

  • Authors:
    • Yoshihito Morimoto
    • Kimihiko Takada
    • Osamu Takeuchi
    • Akinori Takagi
    • Kazuhiro Watanabe
    • Masayoshi Hirohara
    • Tomoyuki Hamamoto
    • Yutaka Masuda
  • View Affiliations / Copyright

    Affiliations: Center for Education and Research on Clinical Pharmacy, Showa Pharmaceutical University, Tokyo 194‑8543, Japan, Biomedical Laboratory, Department of Research, Kitasato Institute Hospital, Tokyo 108‑8642, Japan
  • Pages: 689-699
    |
    Published online on: November 28, 2019
       https://doi.org/10.3892/or.2019.7421
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Abstract

Our previous study demonstrated that gemcitabine (GEM), S‑1, and a combination of GEM and S‑1 (GS) induced S‑phase arrest and increased the phosphorylation of checkpoint kinase 1 (Chk1), which is a critical mediator of cell survival under impaired DNA replication, in pancreatic cancer cell lines. The aim of the present study was to investigate the combined effect of the Chk1 inhibitor prexasertib and antitumor drugs (GEM and S‑1) on pancreatic cancer cell line SUIT‑2. Furthermore, we conducted mechanistic analysis of the combined effect. The MTT assay revealed that a combination of prexasertib and GS showed a strong effect. Mechanistic analysis of the combined effect showed effective induction of apoptosis. Furthermore, a combination of prexasertib and GS downregulated the expression of antiapoptotic protein Bcl‑2. Chk1 knockdown with small interfering RNA and GS treatment resulted in strong induction of apoptosis. Our results provide evidence to show that the combination of prexasertib and GS has a strong antitumor effect and effectively induces apoptosis in pancreatic cancer cells through downregulation of the antiapoptotic protein Bcl‑2. Prexasertib could possibly enhance the effects of standard drugs, including GEM, S‑1, and GS, against pancreatic cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Morimoto Y, Takada K, Takeuchi O, Takagi A, Watanabe K, Hirohara M, Hamamoto T and Masuda Y: Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1. Oncol Rep 43: 689-699, 2020.
APA
Morimoto, Y., Takada, K., Takeuchi, O., Takagi, A., Watanabe, K., Hirohara, M. ... Masuda, Y. (2020). Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1. Oncology Reports, 43, 689-699. https://doi.org/10.3892/or.2019.7421
MLA
Morimoto, Y., Takada, K., Takeuchi, O., Takagi, A., Watanabe, K., Hirohara, M., Hamamoto, T., Masuda, Y."Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1". Oncology Reports 43.2 (2020): 689-699.
Chicago
Morimoto, Y., Takada, K., Takeuchi, O., Takagi, A., Watanabe, K., Hirohara, M., Hamamoto, T., Masuda, Y."Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1". Oncology Reports 43, no. 2 (2020): 689-699. https://doi.org/10.3892/or.2019.7421
Copy and paste a formatted citation
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Spandidos Publications style
Morimoto Y, Takada K, Takeuchi O, Takagi A, Watanabe K, Hirohara M, Hamamoto T and Masuda Y: Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1. Oncol Rep 43: 689-699, 2020.
APA
Morimoto, Y., Takada, K., Takeuchi, O., Takagi, A., Watanabe, K., Hirohara, M. ... Masuda, Y. (2020). Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1. Oncology Reports, 43, 689-699. https://doi.org/10.3892/or.2019.7421
MLA
Morimoto, Y., Takada, K., Takeuchi, O., Takagi, A., Watanabe, K., Hirohara, M., Hamamoto, T., Masuda, Y."Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1". Oncology Reports 43.2 (2020): 689-699.
Chicago
Morimoto, Y., Takada, K., Takeuchi, O., Takagi, A., Watanabe, K., Hirohara, M., Hamamoto, T., Masuda, Y."Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S‑1". Oncology Reports 43, no. 2 (2020): 689-699. https://doi.org/10.3892/or.2019.7421
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