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

초록

Background/Aim: Anti-cancer drug resistance restricts the efficacy of chemotherapy in malignant tumors. Casein kinase 2a (CK2a) is highly expressed in 5fluorouracil (5FU)-resistant colorectal cancer (CRC) cells. We hypothesized that inhibition of CK2a might reduce CRC resistance to 5FU. Materials and Methods: To investigate the role of CK2a 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: CK2a 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 CK2a on endoplasmic reticulum (ER) stress. Combination of CK2a knockdown with 5FU treatment promoted apoptosis of 5FU-resistant CRC cells by inducing ER stress. Conclusion: 5FU treatment in combination with a CK2a inhibitor may exert a synergistic effect against drug-resistant cancer cells.

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