PMID- 25310131
OWN - NLM
STAT- MEDLINE
DCOM- 20150619
LR  - 20211203
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 10
IP  - 6
DP  - 2014 Dec
TI  - Effects of metformin on FOXM1 expression and on the biological behavior of acute 
      leukemia cell lines.
PG  - 3193-8
LID - 10.3892/mmr.2014.2629 [doi]
AB  - 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.
FAU - Zhang, Bing
AU  - Zhang B
AD  - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
FAU - Liu, Long-Long
AU  - Liu LL
AD  - Department of Hematology, Wuhan General Hospital of Guangzhou Military Command, 
      Wuhan, Hubei 430070, P.R. China.
FAU - Mao, Xia
AU  - Mao X
AD  - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
FAU - Zhang, Dong-Hua
AU  - Zhang DH
AD  - Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20141013
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (FOXM1 protein, human)
RN  - 0 (Forkhead Box Protein M1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - HR4S203Y18 (Thiostrepton)
SB  - IM
MH  - Apoptosis/drug effects/genetics
MH  - Cell Cycle Checkpoints/drug effects/genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/genetics
MH  - Cell Transformation, Neoplastic/drug effects/genetics
MH  - Down-Regulation/drug effects/genetics
MH  - Forkhead Box Protein M1
MH  - Forkhead Transcription Factors/*genetics
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Leukemia/*genetics
MH  - Metformin/*pharmacology
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Thiostrepton/pharmacology
EDAT- 2014/10/14 06:00
MHDA- 2015/06/20 06:00
CRDT- 2014/10/14 06:00
PHST- 2013/11/30 00:00 [received]
PHST- 2014/06/17 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2015/06/20 06:00 [medline]
AID - 10.3892/mmr.2014.2629 [doi]
PST - ppublish
SO  - Mol Med Rep. 2014 Dec;10(6):3193-8. doi: 10.3892/mmr.2014.2629. Epub 2014 Oct 13.