The synergistic therapeutic effect of imatinib and protein kinase CK2 Inhibition correlates with PI3K-AKT activation in gastrointestinal stromal tumors - 06/07/22
, Xiangming Mu b Highlights |
• | CK2 was highly expressed in GIST biopsies. |
• | The inhibition of CK2 Inhibited GIST cell viability and promoted apoptosis. |
• | The dual treatment with CX-4945 (CX) and imatinib (IM) were more potent inhibiting GIST cell viability and decreased cell apoptosis compared with mono-treatment. |
• | CK2 inhibition along with Imatinib treatment exhibited synergistic anti-cancer effects on GIST cells by inhibiting PI3K/AKT pathway. |
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.
Conclusion |
Our results demonstrated that inhibition of CK2 combined with IM exhibited a synergistic anti-cancer effect on GIST cells through inactivation of the PI3K/AKT pathway.
Le texte complet de cet article est disponible en PDF.Keywords : Gastrointestinal stromal tumor, CK2, CX-4945, Imatinib, PI3K/AKT pathway
Plan
Vol 46 - N° 6
Article 101886- juin 2022 Retour au numéro
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