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

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

Molecular medicine reports (2019-08-23)
Jingjing Wu, Bin Wei, Yuye Shi, Xueying Lu, Yihan Ding, Chunling Wang, Yufeng Li
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-phospho-Akt1/PKBα (Ser473) Antibody, clone SK703, rabbit monoclonal, culture supernatant, clone SK703, Upstate®
Sigma-Aldrich
Anti-Akt3/PKBγ Antibody, Upstate®, from rabbit
Sigma-Aldrich
Anti-PI3 Kinase Antibody, p85, N-SH3, clone AB6, clone AB6, Upstate®, from mouse