Synergistic effects of LY294002 and ABT199 on the cell cycle in K562, HL60 and KG1a cells.

Abstract

The aim of the present study was to investigate the synergistic effect of LY294002 (a PI3K inhibitor) and ABT199 (a BCL2 inhibitor) on the cell cycle in acute myeloid leukemia (AML). The optimal concentration and duration of combined LY294002 and ABT199 were determined in human erythroleukemia (K562), promyelocytic leukemia (HL60) and myeloid leukemia (KG1a) cell lines. The mRNA and protein expression levels of cell cycle‑related molecules, including S‑phase kinase‑associated protein 2 (Skp2), p27, BCL2, Bax, cleaved caspase 3 (caspase‑3) and caspase 9 (caspase‑9) were detected via reverse transcription‑quantitative PCR and western blot analysis, respectively. At the molecular level, LY294002 and ABT199 combination treatment significantly downregulated Skp2, Bcl2, procaspase‑3 and procaspase‑9 expression levels, but markedly upregulated p27, Bax, cleaved caspase‑3 and caspase‑9 expression levels in K562, HL‑60 and KG1a cells. The results of the present study demonstrated that LY294002 and ABT199 combination treatment may serve as a novel therapeutic strategy for AML.