Open Access

Homoharringtonine enhances the effect of imatinib on chronic myelogenous leukemia cells by downregulating ZFX

  • Authors:
    • Jingjing Wu
    • Bin Wei
    • Yuye Shi
    • Xueying Lu
    • Yihan Ding
    • Chunling Wang
    • Yufeng Li
  • View Affiliations

  • Published online on: July 31, 2019     https://doi.org/10.3892/mmr.2019.10539
  • Pages: 3233-3239
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Homoharringtonine (HHT) and imatinib have a synergistic effect in the clinical treatment of chronic myeloid leukemia (CML). The purpose of the present study was to explore the underlying mechanisms by which HHT enhanced imatinib sensitivity. K562 CML cells were treated with HHT and imatinib separately or in combination. Cell viability was detected by Cell Counting Kit‑8 assay; apoptotic rates and protein expression levels of phosphorylated‑tyrosine (p‑Tyr) and p‑CRK like proto‑oncogene, adaptor protein (p‑Crkl) were analyzed by flow cytometry; zinc‑finger protein, X‑linked (ZFX) overexpression plasmid was transfected to cells using electroporation; western blotting was used to detect the protein expression levels of PI3K, AKT, p‑AKT and ZFX; and reverse transcription‑quantitative PCR was used to measure ZFX mRNA expression levels. The results demonstrated that HHT and imatinib co‑treatment had significant effects of proliferation inhibition and apoptosis induction on K562 CML cells compared with imatinib alone. Co‑treatment also significantly downregulated the expression levels of p‑Tyr, p‑Crkl, PI3K and p‑Akt compared with imatinib or HHT treatment. In addition, HHT downregulated ZFX mRNA and protein expression. ZFX overexpression reversed cell sensitivity to imatinib and HHT and also reduced the HHT‑induced imatinib sensitization by increasing p‑Akt expression. In conclusion, HHT may enhance the effect of imatinib on CML cells by downregulating ZFX.

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October 2019
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Copy and paste a formatted citation
APA
Wu, J., Wei, B., Shi, Y., Lu, X., Ding, Y., Wang, C., & Li, Y. (2019). Homoharringtonine enhances the effect of imatinib on chronic myelogenous leukemia cells by downregulating ZFX. Molecular Medicine Reports, 20, 3233-3239. https://doi.org/10.3892/mmr.2019.10539
MLA
Wu, J., Wei, B., Shi, Y., Lu, X., Ding, Y., Wang, C., Li, Y."Homoharringtonine enhances the effect of imatinib on chronic myelogenous leukemia cells by downregulating ZFX". Molecular Medicine Reports 20.4 (2019): 3233-3239.
Chicago
Wu, J., Wei, B., Shi, Y., Lu, X., Ding, Y., Wang, C., Li, Y."Homoharringtonine enhances the effect of imatinib on chronic myelogenous leukemia cells by downregulating ZFX". Molecular Medicine Reports 20, no. 4 (2019): 3233-3239. https://doi.org/10.3892/mmr.2019.10539