The journey of metformin from glycaemic control to mTOR inhibition and the suppression of tumour growth

被引:84
作者
Amin, Sam [1 ]
Lux, Andrew [1 ]
O'Callaghan, Finbar [2 ]
机构
[1] Univ Hosp Bristol, Upper Maudlin St Ctr Level 6, Bristol BS2 8AE, Avon, England
[2] UCL, Inst Child Hlth, London WC1N 1EH, England
关键词
clinical pharmacology; genetic polymorphism; genetics and pharmacogenetics; neurology; therapeutics; TUBEROUS SCLEROSIS COMPLEX; ANTIDIABETIC DRUG METFORMIN; NITRIC-OXIDE SYNTHASE; LEARNING-DISABILITY; COGNITIVE FUNCTION; SKELETAL-MUSCLE; BLOOD-PRESSURE; DOUBLE-BLIND; CELL-DEATH; IN-VIVO;
D O I
10.1111/bcp.13780
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Our knowledge of the effect of metformin on human health is increasing. In addition to its ability to improve the control of hyperglycaemia, metformin has been shown to reduce the burden o,f ageing via effects on damaged DNA and the process of apoptosis. Studies have shown that metformin may reduce the risk of cardiovascular disease through influences on body weight, blood pressure, cholesterol levels and the progression of atherosclerosis. Studies also suggest that metformin may be beneficial for neuro-psychiatric disorders, cognitive impairment and in reducing the risk of dementia, erectile dysfunction and Duchenne muscular dystrophy. In vivo and in vitro studies have shown that metformin has anti-cancer properties, and population studies have suggested that metformin may reduce the risk of cancer or improve cancer prognosis. It is thought that it exerts its anti-cancer effect through the inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. Because of its effect on the mTOR pathway, there may be a role for metformin in slowing or reversing growth of life-threatening hamartomas in tuberous sclerosis complex.
引用
收藏
页码:37 / 46
页数:10
相关论文
共 84 条
[1]   Repositioning metformin in cancer: genetics, drug targets, and new ways of delivery [J].
Aldea, Mihaela ;
Craciun, Lucian ;
Tomuleasa, Ciprian ;
Berindan-Neagoe, Ioana ;
Kacso, Gabriel ;
Florian, Ioan Stefan ;
Crivii, Carmen .
TUMOR BIOLOGY, 2014, 35 (06) :5101-5110
[2]   Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase [J].
Algire, Carolyn ;
Amrein, Lilian ;
Zakikhani, Mahvash ;
Panasci, Lawrence ;
Pollak, Michael .
ENDOCRINE-RELATED CANCER, 2010, 17 (02) :351-360
[3]  
Amin S, 2018, ARCH DIS CHILD, V103
[4]   Therapeutic Trial of Metformin and Bortezomib in a Mouse Model of Tuberous Sclerosis Complex (TSC) [J].
Auricchio, Neil ;
Malinowska, Izabela ;
Shaw, Reuben ;
Manning, Brendan D. ;
Kwiatkowski, David J. .
PLOS ONE, 2012, 7 (02)
[5]   The ROS production induced by a reverse-electron flux at respiratory-chain complex 1 is hampered by metformin [J].
Batandier, Cecile ;
Guigas, Bruno ;
Detaille, Dominique ;
El-Mir, M-Yehia ;
Fontaine, Eric ;
Rigoulet, Michel ;
Leverve, Xavier M. .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 2006, 38 (01) :33-42
[6]   Pharmacokinetics, tissue distribution and relative bioavailability of isoniazid-solid lipid nanoparticles [J].
Bhandari, Rohit ;
Kaur, Indu Pal .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2013, 441 (1-2) :202-212
[7]   Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis [J].
Bissler, John J. ;
McCormack, Francis X. ;
Young, Lisa R. ;
Elwing, Jean M. ;
Chuck, Gail ;
Leonard, Jennifer M. ;
Schmithorst, Vincent J. ;
Laor, Tal ;
Brody, Alan S. ;
Bean, Judy ;
Salisbury, Shelia ;
Franz, David N. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (02) :140-151
[8]   Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study [J].
Bissler, John J. ;
Kingswood, J. Chris ;
Radzikowska, Elzbieta ;
Zonnenberg, Bernard A. ;
Belousova, Elena ;
Frost, Michael D. ;
Sauter, Matthias ;
Brakemeier, Susanne ;
de Vries, Petrus J. ;
Berkowitz, Noah ;
Voi, Maurizio ;
Peyrard, Severine ;
Budde, Klemens .
PLOS ONE, 2017, 12 (08)
[9]   Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial [J].
Bissler, John J. ;
Kingswood, J. Christopher ;
Radzikowska, Elzbieta ;
Zonnenberg, Bernard A. ;
Frost, Michael ;
Belousova, Elena ;
Sauter, Matthias ;
Nonomura, Norio ;
Brakemeier, Susanne ;
de Vries, Petrus J. ;
Whittemore, Vicky H. ;
Chen, David ;
Sahmoud, Tarek ;
Shah, Gaurav ;
Lincy, Jeremie ;
Lebwohl, David ;
Budde, Klemens .
LANCET, 2013, 381 (9869) :817-824
[10]   Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC [J].
Blandino, Giovanni ;
Valerio, Mariacristina ;
Cioce, Mario ;
Mori, Federica ;
Casadei, Luca ;
Pulito, Claudio ;
Sacconi, Andrea ;
Biagioni, Francesca ;
Cortese, Giancarlo ;
Galanti, Sergio ;
Manetti, Cesare ;
Citro, Gennaro ;
Muti, Paola ;
Strano, Sabrina .
NATURE COMMUNICATIONS, 2012, 3