The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line

  • Authors:
    • Chengji Jin
    • Ping Song
    • Ji Pang
  • View Affiliations

  • Published online on: August 1, 2019     https://doi.org/10.3892/ol.2019.10696
  • Pages: 3845-3856
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Lung cancer negatively impacts global health, and the incidence of non‑small cell lung cancer (NSCLC) is highest among all forms of lung cancer. Chemotherapy failure mainly occurs due to drug resistance; however, the associated molecular mechanism remains unclear. Casein kinase II (CK2), which plays important roles in the occurrence, development and metastasis of many tumours, regulates Wnt signaling by modulating β‑catenin expression. In the present study the effects of the CK2 inhibitor, CX4945 on cisplatin [or cis‑diamminedichloroplatinum (II); (DDP)]‑resistant A549 cells (A549/DDP) were investigated to elucidate the underlying molecular mechanism. A549/DDP cells were divided into four groups (blank control, CX4945, cisplatin and CX4945+cisplatin). Cisplatin resistance was 5.16‑fold greater in A549/DDP cells compared with that in A549 cells, with an optimal cisplatin concentration of 5 µg/ml. Moreover, levels of CK2, dishevelled‑2 (DVL‑2) phosphorylated (p) at Ser143 (p‑DVL‑2Ser143), and major Wnt‑signaling proteins were significantly higher in A549/DDP cells compared with that in A549 cells (P<0.05), with these levels further increased following cisplatin treatment (P<0.05), whereas these levels significantly decreased in A549 cells after cisplatin treatment (P<0.05). Additionally, multidrug‑resistance‑associated protein 1 and lung resistance protein expression was significantly higher in A549/DDP cells compared with that in A549 cells (P<0.05), with these levels increasing further in A549/DDP (P<0.05) but not A549 cells upon cisplatin treatment (P>0.05). In addition, reduced expression of resistance proteins in A549/DDP cells was accompanied by a decline in the 50% growth inhibition after CX4945 pre‑treatment. Furthermore, levels of p‑DVL‑2Ser143 and major Wnt‑signaling proteins decreased significantly after treatment of A549/DDP cells with CX4945+cisplatin, whereas DVL‑2 and p‑DVL‑2Thr224 levels remained unchanged. Additionally, significant elevations in apoptosis rates in the CX4945+cisplatin group relative to the control and cisplatin‑only groups, was observed (P<0.001). These results suggested that inhibiting Wnt/β‑catenin signaling with CX4945, which attenuates levels of drug‑resistance‑associated proteins and induces apoptosis, might reverse cisplatin resistance in NSCLC.

Related Articles

Journal Cover

October 2019
Volume 18 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Jin, C., Song, P., & Pang, J. (2019). The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line. Oncology Letters, 18, 3845-3856. https://doi.org/10.3892/ol.2019.10696
MLA
Jin, C., Song, P., Pang, J."The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line". Oncology Letters 18.4 (2019): 3845-3856.
Chicago
Jin, C., Song, P., Pang, J."The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line". Oncology Letters 18, no. 4 (2019): 3845-3856. https://doi.org/10.3892/ol.2019.10696