Idelalisib induces G1 arrest and apoptosis in chronic myeloid leukemia K562 cells.

Increasing resistance of imatinib, a BCR-ABL tyrosine kinase inhibitor, hinders its use in the therapy of chronic myeloid leukemia (CML). The PI3K pathway is known to be closely involved in BCR-ABL transformation and the tumorigenesis of CML, suggesting that PI3K may be a potential target for CML therapy. Idelalisib, a specific inhibitor of PI3K p110δ, has been approved for the treatment of chronic lymphocytic leukemia (CLL). However, the antileukemia effect of idelalisib on CML remains unknown. In the present study, the antileukemia activity of idelalisib alone or in combination with imatinib was investigated by use of K562 cells. Idelalisib inhibited K562 proliferation in a dose-dependent manner. G1 arrest was induced, in which upregulation of p27 and p21, as well as downregulation of cyclin D1 and p-pRb, may be involved. Furthermore, idelalisib induced apoptosis in the K562 cells, with increased expression of pro-apoptotic molecules such as Bad and Bax, cleavage of caspase-9, -8 and -3, and PARP, in contrast to downregulation of anti-apoptotic protein Bcl-2. Combination of idelalisib with imatinib led to a synergistic antiproliferative effect on K562 cells, together with enhanced activity of G1 arrest and apoptosis induction. In conclusion, idelalisib exhibited in vitro antitumor activity on CML K562 cells alone or in combination with imatinib, suggesting potential application in CML therapy.