title: Effects of metformin on FOXM1 expression and on 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.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, Hubei 430070, P.R. China.
authors.forename: Long-Long
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008687:Metformin / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics; D013883:Thiostrepton / Q000494:pharmacology
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D008687:Metformin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D013883:Thiostrepton