Casein Kinase 2α Enhances 5-Fluorouracil Resistance in Colorectal Cancer Cells by Inhibiting Endoplasmic Reticulum Stress

Abstract

Background/aim: Anti-cancer drug resistance restricts the efficacy of chemotherapy in malignant tumors. Casein kinase 2α (CK2α) is highly expressed in 5-fluorouracil (5FU)-resistant colorectal cancer (CRC) cells. We hypothesized that inhibition of CK2α might reduce CRC resistance to 5FU.

Materials and methods: To investigate the role of CK2α in 5FU-resistant CRC cells, we assessed cell viability, apoptosis, cyclin-dependent kinase 4 (CDK4) activity, cell-cycle progression, invasion, and sphere formation in 5FU-resistant CRC cells.

Results: CK2α levels were significantly increased in 5FU-resistant CRC cells compared to those in wild-type CRC cells. During exposure to 5FU, viability, CDK4 activity, cell-cycle progression, invasion, and sphere formation were enhanced, while apoptosis was decreased in 5FU-resistant CRC cells. These effects were mediated by the inhibiting effects of CK2α on endoplasmic reticulum (ER) stress. Combination of CK2α knockdown with 5FU treatment promoted apoptosis of 5FU-resistant CRC cells by inducing ER stress.

Conclusion: 5FU treatment in combination with a CK2α inhibitor may exert a synergistic effect against drug-resistant cancer cells.

Keywords: 5-fluorouracil; CK2α; Colorectal cancer; ER stress; anti-cancer drug resistance.