Open Access

CX‑5461 potentiates imatinib‑induced apoptosis in K562 cells by stimulating KIF1B expression

  • Authors:
    • Chaochao Dai
    • Xiaopei Cui
    • Jie Wang
    • Bo Dong
    • Haiqing Gao
    • Mei Cheng
    • Fan Jiang
  • View Affiliations

  • Published online on: January 18, 2024     https://doi.org/10.3892/etm.2024.12395
  • Article Number: 107
  • Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The selective RNA polymerase I inhibitor CX‑5461 has been shown to be effective in treating some types of leukemic disorders. Emerging evidence suggests that combined treatments with CX‑5461 and other chemotherapeutic agents may achieve enhanced effectiveness as compared with monotherapies. Currently, pharmacodynamic properties of the combination of CX‑5461 with tyrosine kinase inhibitors remain to be explored. The present study tested whether CX‑5461 could potentiate the effect of imatinib in the human chronic myeloid leukemia cell line K562, which is p53‑deficient. It was demonstrated that CX‑5461 at 100 nM, which was non‑cytotoxic in K562 cells, potentiated the pro‑apoptotic effect of imatinib. Mechanistically, the present study identified that the upregulated expression of kinesin family member 1B (KIF1B) gene might be involved in mediating the pro‑apoptotic effect of imatinib/CX‑5461 combination. Under the present experimental settings, however, neither CX‑5461 nor imatinib alone exhibited a significant effect on KIF1B expression. Moreover, using other leukemic cell lines, it was demonstrated that regulation of KIF1B expression by imatinib/CX‑5461 was not a ubiquitous phenomenon in leukemic cells and should be studied in a cell type‑specific manner. In conclusion, the results suggested that the synergistic interaction between CX‑5461 and imatinib may be of potential clinical value for the treatment of tyrosine kinase inhibitor‑resistant chronic myeloid leukemia.
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March-2024
Volume 27 Issue 3

Print ISSN: 1792-0981
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Spandidos Publications style
Dai C, Cui X, Wang J, Dong B, Gao H, Cheng M and Jiang F: CX‑5461 potentiates imatinib‑induced apoptosis in K562 cells by stimulating <em>KIF1B</em> expression. Exp Ther Med 27: 107, 2024
APA
Dai, C., Cui, X., Wang, J., Dong, B., Gao, H., Cheng, M., & Jiang, F. (2024). CX‑5461 potentiates imatinib‑induced apoptosis in K562 cells by stimulating <em>KIF1B</em> expression. Experimental and Therapeutic Medicine, 27, 107. https://doi.org/10.3892/etm.2024.12395
MLA
Dai, C., Cui, X., Wang, J., Dong, B., Gao, H., Cheng, M., Jiang, F."CX‑5461 potentiates imatinib‑induced apoptosis in K562 cells by stimulating <em>KIF1B</em> expression". Experimental and Therapeutic Medicine 27.3 (2024): 107.
Chicago
Dai, C., Cui, X., Wang, J., Dong, B., Gao, H., Cheng, M., Jiang, F."CX‑5461 potentiates imatinib‑induced apoptosis in K562 cells by stimulating <em>KIF1B</em> expression". Experimental and Therapeutic Medicine 27, no. 3 (2024): 107. https://doi.org/10.3892/etm.2024.12395