文章标题：The synergistic therapeutic effect of imatinib and protein kinase CK2 Inhibition correlates with PI3K-AKT activation in gastrointestinal stromal tumors
期刊：Clinics and Research in Hepatology and Gastroenterology
作者列表：Linsen Zhou, Hao Wang, Haofeng Liu, Zhijun Huang, Zhiqiang Wang, Xiaojun Zhou, Xiangming Mu
发表时间：2022-2-18
影响因子：3.189
DOI:10.1016/j.clinre.2022.101886
主要研究成果：Abstract
Background
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Casein kinase 2 (CK2) has been reported to be involved in several cellular processes in multiple cancers. However, the role of CK2 in GIST remains unclear.
Aim
We aimed to investigate the combinatorial treatment of imatinib (IM) and CK2 inhibition on the progression of GISTs.
Methods
GIST biopsies and adjacent normal tissues were collected from patients. GIST882 and GIST48 cell lines were subjected to investigate the effect of IM and CK2 inhibition in GIST cells. CCK-8 assay, Caspase-3 activity assay, western blotting, and flow cytometry analysis were employed in the present investigation.
Results
Our results showed that CK2 was highly expressed in GIST biopsies, and inhibition of CK2 resulted in decrease in cell viability and increase in apoptosis of GIST cells. Moreover, the combination treatment with CX-4945 (CX) and IM resulted in a more significant decrease in cell viability and increase in cell apoptosis compared with mono-treatment. Mechanistically, the combination treatment influenced the activation of the PI3K/AKT pathway. The activation of the PI3K/AKT pathway reversed the synergistic impacts of the combined treatment on cell viability and apoptosis.
