Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
University of Ulsan Digestive Diseases Research Center, Seoul, Republic of Korea.
Anticancer Res. 2022 Jul;42(7):3435-3443. doi: 10.21873/anticanres.15830.
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.
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.
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.
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.
背景/目的：酪蛋白激酶 2（CK2）是一种生存促进蛋白激酶，通过调节细胞周期和细胞凋亡参与细胞生长/增殖。CK2 在各种癌症中过度表达，与预后不良相关。本研究探讨了 CK2 抑制剂 silmitasertib（CX-4945）对胆管癌（CCA）细胞的抗癌作用。
评估 CX-4945 对人胆管癌细胞系 TFK-1 和 SSP-25 的细胞活力、细胞周期阻滞和细胞凋亡的影响。通过蛋白质印迹法评估翻译后修饰和细胞周期调节剂（包括 p21、Polo 样激酶 1（PLK1）和 p53）水平的变化。使用碘化丙啶/膜联蛋白 V 染色检测凋亡反应。
暴露于 CX-4945 的 TFK-1 和 SSP-25 细胞表现出形态变化，细胞活力下降超过 50%（p<0.05）。细胞周期阻滞在 G2 期检测到，磷酸化 PLK1 和 p21 增加。此外，磷酸化 PLK1 诱导 p53 的降解，导致 Bax 从 Bcl-xL 解离。CX-4945 处理还诱导 Caspase3 和 PARP 的切割。
CX-4945 通过调节 PLK1 和 p53 诱导胆管癌细胞周期阻滞和细胞死亡。这可能为晚期胆管癌提供一种新的治疗策略。
