Effects of metformin on FOXM1 expression andon the biological behavior of acute leukemia cell lines

Abstract

Forkhead box M1 (FOXM1) is a typical proliferation-associated transcription factor, which is overexpressed in many types of human cancer. We investigated the expression level of FOXM1 in patients with untreated acute leukemia (AL) and explored the correlation between expression levels and AL type. The relationship between the expression of the genes FOXM1 and mammalian target of rapamycin (mTOR) was determined after treatment of ML-2 cells with thiostrepton. The apoptosis, proliferation and cell-cycle progression of ML-2 lines were examined after treatment with metformin. We found that FOXM1 is expressed in the majority of AL patients and that its expression level was associated with the AL type. Thiostrepton is a specific inhibitor of FOXM1, and by inhibiting the FOXM1 expression via thiostrepton, we observed downregulatiion of mTOR; a significant correlation between FOXM1 and mTOR levels was observed. Thus, metformin may be involved in the downregulation of FOXM1. In addition, our study demonstrated that metformin promotes the apoptosis of ML-2 cells, induces cell-cycle arrest at the G0/G1 and G2/M phases, and inhibits proliferation. The potential role of FOXM1 in tumorigenesis renders it an attractive target for anticancer therapy, and metformin may represent a new agent for the treatment of leukemia.