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The Casein Kinase 2 Inhibitor CX-4945 Promotes Cholangiocarcinoma Cell Death Through PLK1.
Lee, DA Sol; Lee, Seonmin; Kim, Chorong; Kim, Danbee; Kim, Kyu-Pyo; Yoo, Changhoon.
Afiliação
  • Lee DS; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
  • Lee S; University of Ulsan Digestive Diseases Research Center, Seoul, Republic of Korea.
  • Kim C; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
  • Kim D; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Kim KP; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Yoo C; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea yooc@amc.seoul.kr.
Anticancer Res ; 42(7): 3435-3443, 2022 Jul.
Article em En | MEDLINE | ID: mdl-35790285
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias dos Ductos Biliares / Colangiocarcinoma Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias dos Ductos Biliares / Colangiocarcinoma Idioma: En Ano de publicação: 2022 Tipo de documento: Article