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

Cholangiocarcinoma is an aggressive malignancy with high mortality, and effective therapeutic agents for this cancer are limited. Cyclindependent 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 cyclindependent kinase 1 (pCDK1), pCDK2, cyclin B1, and cyclin E1 in carcinoma cells. The nuclear expression of pCDK1 and cyclin B1 was positively correlated with the presence of lymph node metastasis and the clinical stage, and pCDK1 expression was also associated with poor patient survival. The treatment of human cholangiocarcinoma cell lines (CCKS1, TFK1 and HUCCT1) with the multiCDK inhibitor roscovitine decreased pCDK1 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 pCDK1 may be a useful prognostic marker of cholangiocarcinoma.