CK2 inhibitor CX4945 reverses cisplatin-resistance of lung cancer A549/DDP cells
10.3781/j.issn.1000-7431.2019.11.639
- Author:
Chengji JIN
1
Author Information
1. Department of Respiratory Medicine, Affiliated Hospital of Jiangsu University
- Publication Type:Journal Article
- Keywords:
Carcinoma;
Casein kinase 2;
Cisplatin;
CX4945;
Drug resistance;
Neoplasm;
Non-small cell lung;
Wnt signaling pathway
- From:
Tumor
2019;39(1):10-18
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of CK2 (casein kinase 2) inhibitor CX4945 on the cisplatin (DDP)-resistance of lung cancer A549/DDP cells and the underlying molecular mechanism. Methods: The CCK-8 assay was used to detect the half maximal inhibitory concentration (IC50) of DDP in lung cancer A549 and A549/DDP cells, and to compare the DDP-resistance of two cell lines. The effect of CX4945 on DDP-resistance of A549/DDP cells was tested by CCK-8 method. Western blotting was used to detect the expressions of Wnt signaling pathway-related proteins (CK2α, β-catenin and cyclin D1), drug resistance-related proteins [multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP)] and apoptosis-related protein [cleaved caspase-3 (c-caspase-3)] in A549 and A549/DDP cells treated with DDP or not. The A549/DDP cells were treated with no drug (as the control group), CX4945, DDP and their combination (as CX4945+DDP group), then the expressions of Wnt signaling pathway-, drug resistance- and apoptosis-related proteins were detected by Western blotting, and the apoptosis of A549/DDP cells was detected by FCM method. Results: The IC50 value of DDP in A549/DDP cells was 4.59 times higher than that in A549 cells, and the DDP-resistance of A549/DDP cells was decreased by CX4945 pretreatment (P < 0.001). The expression levels of CK2α, β-catenin, cyclin D1, MRP1 and LRP proteins were significantly increased in A549/DDP cells as compared with A549 cells (all P < 0.001), and the levels of these proteins in A549/DDP cells were further increased after DDP treatment (all P < 0.001). In A549 cells after treatment with DDP, the expression levels of CK2α, β-catenin and cyclin D1 proteins were reduced (all P < 0.01), but the levels of MRP1 and LRP proteins were not significantly changed (both P > 0.05). Compared with the control group and DDP group, the expression levels of β-catenin, cyclin D1, MRP1 and LRP proteins in A549/DDP cells of CX4945 group and CX4945+DDP group were significantly declined (all P < 0.01). In addition, the apoptosis rate of A549/DDP cells and the expression level of c-caspase-3 in CX4945+DDP group were significantly higher than those in the control group and DDP group (all P < 0.001). Conclusion: CK2 inhibitor CX4945 can reverse the DDP resistance of lung cancer A549/ DDP cells through blocking Wnt signal pathway and decreasing the expressions of drug resistance-relatied proteins.
