The cyclin‑dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma

  • Authors:
    • Minako Yamamura
    • Yasunori Sato
    • Kenta Takahashi
    • Motoko Sasaki
    • Kenichi Harada
  • View Affiliations

  • Published online on: November 8, 2019     https://doi.org/10.3892/or.2019.7405
  • Pages: 306-317
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Abstract

Cholangiocarcinoma is an aggressive malignancy with high mortality, and effective therapeutic agents for this cancer are limited. Cyclin‑dependent kinase (CDK) pathways are therapeutic targets for various types of cancers; however, their involvement in cholangiocarcinoma remains unclear. The present study examined the biological significance of CDK pathways in cholangiocarcinoma. An immunohistochemical analysis of cholangiocarcinoma tissue sections revealed the upregulated expression of phosphorylated cyclin‑dependent kinase 1 (p‑CDK1), p‑CDK2, cyclin B1, and cyclin E1 in carcinoma cells. The nuclear expression of p‑CDK1 and cyclin B1 was positively correlated with the presence of lymph node metastasis and the clinical stage, and p‑CDK1 expression was also associated with poor patient survival. The treatment of human cholangiocarcinoma cell lines (CCKS‑1, TFK‑1 and HUCCT‑1) with the multi‑CDK inhibitor roscovitine decreased p‑CDK1 expression, inhibited cell proliferation, arrested the cell cycle at the G1 or G2/M phase, and significantly inhibited carcinoma cell invasion. In vivo studies using a murine xenograft model revealed that an intraperitoneal injection of roscovitine significantly inhibited cholangiocarcinoma cell growth. Roscovitine induced apoptosis in cholangiocarcinoma cells in vitro and in vivo. These results demonstrated the potential of the CDK pathway involving CDK1 as a therapeutic target for cholangiocarcinoma. Furthermore, the immunohistochemical expression of p‑CDK1 may be a useful prognostic marker of cholangiocarcinoma.
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January-2020
Volume 43 Issue 1

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

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Spandidos Publications style
Yamamura M, Sato Y, Takahashi K, Sasaki M and Harada K: The cyclin‑dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma. Oncol Rep 43: 306-317, 2020
APA
Yamamura, M., Sato, Y., Takahashi, K., Sasaki, M., & Harada, K. (2020). The cyclin‑dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma. Oncology Reports, 43, 306-317. https://doi.org/10.3892/or.2019.7405
MLA
Yamamura, M., Sato, Y., Takahashi, K., Sasaki, M., Harada, K."The cyclin‑dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma". Oncology Reports 43.1 (2020): 306-317.
Chicago
Yamamura, M., Sato, Y., Takahashi, K., Sasaki, M., Harada, K."The cyclin‑dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma". Oncology Reports 43, no. 1 (2020): 306-317. https://doi.org/10.3892/or.2019.7405