In patients with
chronic myelogenous leukemia (CML), resistance to
tyrosine kinase inhibitor (TKI)
therapy, like
imatinib, can cause death, progression to accelerated phase or
blast crises, and the need for maintenance treatment.
Icaritin is an active component of the genus Epimedium, a traditional Chinese herbal medicine.
Icaritin has been shown to notably inhibit the growth of CML cells. To explore the potential mechanisms of inhibiting growth and inducing cell senescence in
imatinib-resistant CML cells by
icaritin, MTT assays were used to assess the cell viability. The apoptosis and cell cycle arrest were evaluated using flow cytometry. The SA-β-Gal staining and the intracellular
reactive oxygen species (ROS) production were measured using flow cytometry to detect the senescent cells. qRT-PCR was conducted to assess the expression of the cell cycle-associated
proteins, and western blotting was used to analyze the expressions of the JAK2 and STAT3 phosphorylation
proteins. The results showed that
icaritin inhibited cell growth and induced cell senescence in
imatinib-resistant CML cells, which is associated with the regulation of the JAK2/STAT3/P21 axis and accompanied by the accumulation of ROS. Our data suggest that
icaritin is a promising therapeutic strategy for the treatment of
imatinib-resistant patients with CML.