Inhibition of protein kinase CK2 sensitizes non-small cell lung cancer cells to cisplatin via upregulation of PML

Mol Cell Biochem. 2017 Dec;436(1-2):87-97. doi: 10.1007/s11010-017-3081-2. Epub 2017 Jul 25.

Abstract

Non-small cell lung carcinoma (NSCLC), a malignancy of lungs, is very aggressive and usually ends up with a dismal prognosis. Cisplatin (CDDP)-based systemic chemotherapy is the main pharmaceutical approach for treating NSCLC, but its effect is discounted by some hitherto unknown reasons. Thus, this study is dedicated to improving the efficacy of CDDP. Our results show that combining use of CDDP with CK2 siRNA or inhibitor is more efficient in suppressing cancer cell growth and promoting apoptosis than use of CDDP alone. The underlying mechanism is that CDDP has two pathways to go: one is that it directly induces apoptosis and the other is that it activates CK2, which suppresses proapoptosis gene promyelocytic leukemia (PML). In conclusion, inhibiting CK2 can enhance sensitivity of CDDP to NSCLC cancer cells through PML.

Keywords: CDDP; CK2; NSCLC; PML.

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Casein Kinase II / antagonists & inhibitors*
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism
  • Cisplatin / pharmacology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Promyelocytic Leukemia Protein / biosynthesis*
  • Promyelocytic Leukemia Protein / genetics
  • Protein Kinase Inhibitors / pharmacology*
  • Up-Regulation / drug effects*

Substances

  • Promyelocytic Leukemia Protein
  • Protein Kinase Inhibitors
  • PML protein, human
  • Casein Kinase II
  • Cisplatin