Metformin inhibits leptin-induced growth and migration of glioblastoma cells

  • Authors:
    • Rita Ferla
    • Eva Haspinger
    • Eva Surmacz
  • View Affiliations

  • Published online on: August 3, 2012     https://doi.org/10.3892/ol.2012.843
  • Pages: 1077-1081
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Abstract

Metformin, a derivative of biguanide, is a first-line therapy for type 2 diabetes mellitus. Since the drug has been shown to significantly reduce the risk of various cancers and cancer mortality in diabetic patients, it is being considered as a potential anticancer therapeutic or preventive agent. In cellular models, metformin inhibits the growth of many types of cancer cells; however, its effects on glioblastoma multiforme (GBM) are not well characterized. Here, we analyzed the effects of metformin on the growth and migration of LN18 and LN229 GBM cells cultured under basal conditions or exposed to leptin, a cytokine that has recently been implicated in GBM development. We found that 2-16 mM metformin reduced basal and leptin-stimulated growth of GBM cells in a dose-dependent manner. Furthermore, the drug significantly inhibited the migration of GBM cells. The action of metformin was mediated through the upregulation of its main signaling molecule, the adenosine monophosphate-activated protein kinase (AMPK), as well as through the downregulation of the signal transducer and activator of transcription 3 (STAT3) and the Akt/PKB serine/threonine protein kinase. In leptin-treated cells, the drug reversed the effects of the cytokine on the AMPK and STAT3 pathways, but modulated Akt activity in a cell-dependent manner. Our results suggest that metformin or similar AMPK-targeting agents with optimized blood-brain-barrier penetrability could be developed as potential treatments of GBM and could be used in conjunction with other target drugs such as leptin receptor antagonists.
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November 2012
Volume 4 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Ferla R, Haspinger E and Surmacz E: Metformin inhibits leptin-induced growth and migration of glioblastoma cells. Oncol Lett 4: 1077-1081, 2012
APA
Ferla, R., Haspinger, E., & Surmacz, E. (2012). Metformin inhibits leptin-induced growth and migration of glioblastoma cells. Oncology Letters, 4, 1077-1081. https://doi.org/10.3892/ol.2012.843
MLA
Ferla, R., Haspinger, E., Surmacz, E."Metformin inhibits leptin-induced growth and migration of glioblastoma cells". Oncology Letters 4.5 (2012): 1077-1081.
Chicago
Ferla, R., Haspinger, E., Surmacz, E."Metformin inhibits leptin-induced growth and migration of glioblastoma cells". Oncology Letters 4, no. 5 (2012): 1077-1081. https://doi.org/10.3892/ol.2012.843