PT  - JOURNAL ARTICLE
AU  - LEE, DA SOL
AU  - LEE, SEONMIN
AU  - KIM, CHORONG
AU  - KIM, DANBEE
AU  - KIM, KYU-PYO
AU  - YOO, CHANGHOON
TI  - The Casein Kinase 2 Inhibitor CX-4945 Promotes Cholangiocarcinoma Cell Death Through PLK1
AID  - 10.21873/anticanres.15830
DP  - 2022 Jul 01
TA  - Anticancer Research
PG  - 3435--3443
VI  - 42
IP  - 7
4099  - http://ar.iiarjournals.org/content/42/7/3435.short
4100  - http://ar.iiarjournals.org/content/42/7/3435.full
SO  - Anticancer Res2022 Jul 01; 42
AB  - Background/Aim: Casein Kinase 2 (CK2) is a prosurvival protein kinase involved in cell growth/proliferation through the regulation of the cell cycle and apoptosis. CK2 is over-expressed in various cancers, which correlates with a poor prognosis. This study examined the anti-cancer effects of silmitasertib (CX-4945), a CK2 inhibitor, on cholangiocarcinoma (CCA) cells. Materials and Methods: The effects of CX-4945 on cell viability, cell cycle arrest, and apoptosis in the human cholangiocarcinoma cell lines TFK-1 and SSP-25 were evaluated. Alterations in posttranslational modifications and the levels of cell cycle regulators including p21, Polo-like kinase 1 (PLK1), andp53 were assessed by western blotting. Apoptotic responses were examined using Propidium iodine/Annexin V staining. Results: TFK-1 and SSP-25 cells exposed to CX-4945 showed morphologic changes and a more than 50% decrease in cell viability (p<0.05). Cell cycle arrest at the G2 phase was detected following an increase in phosphorylated PLK1 and p21. Furthermore, phospho-PLK1 induced the degradation of p53, which led to the dissociation of Bax from Bcl-xL. The cleavage of Caspase3 and PARP were also induced by CX-4945 treatment. Conclusion: CX-4945 induces cell cycle arrest and cell death in cholangiocarcinoma cells via the regulation of PLK1 and p53. This may provide a novel therapeutic strategy for advanced cholangiocarcinoma.