Casein Kinase 2α Augments Oxaliplatin Resistance in Colorectal Cancer Cells by Increasing ABCE1 Expression

Anticancer Res. 2023 Jun;43(6):2519-2525. doi: 10.21873/anticanres.16419.

Abstract

Background/aim: Antitumor drug resistance is a major hurdle in treating patients with malignant tumors. Casein kinase 2α (CK2α) expression is highly enhanced in oxaliplatin-resistant CRC cells. We investigated whether CK2α expression is associated with oxaliplatin resistance in CRC cells.

Materials and methods: To determine the effect of CK2α on drug resistance in CRC, we assessed the cell viability, adenosine triphosphate-binding cassette (ABC) transporter expression, apoptosis, and sphere formation according to CK2α expression in oxaliplatin-resistant CRC cells.

Results: CK2α expression was significantly increased in oxaliplatin-resistant CRC cells compared with that in wild-type CRC cells. In addition, the mRNA expression of ABC transporters, including ABCA12, ABCC2, and ABCE1, was significantly enhanced in oxaliplatin-resistant CRC cells, whereas this effect was blocked by the knockdown of CK2α. Furthermore, a cell viability test showed that oxaliplatin resistance was inhibited by decreasing CK2α expression, resulting in the induction of apoptosis and suppression of sphere formation.

Conclusion: CK2α regulates cell survival, apoptosis, sphere formation, and drug resistance in oxaliplatin-resistant CRC cells by regulating ABC transporters. Therefore, targeting CK2α in drug-resistant CRC cells may be a novel strategy for treating patients with CRC.

Keywords: ABC transporter; CK2α; anti-tumor drug resistance; colorectal cancer cells; oxaliplatin.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Casein Kinase II*
  • Cell Line, Tumor
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Drug Resistance, Neoplasm*
  • Humans
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use

Substances

  • ABCE1 protein, human
  • ATP-Binding Cassette Transporters
  • Casein Kinase II
  • Oxaliplatin