June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Metformin inhibits survival, migration, and vascular endothelial growth factor production in uveal melanoma cells
Author Affiliations & Notes
  • Bruna Duarte Moron de Andrade
    MUHC - McGill University Ocular Pathology Laboratory, Montreal, Quebec, Canada
  • Jade Lasiste
    MUHC - McGill University Ocular Pathology Laboratory, Montreal, Quebec, Canada
  • Denise Miyamoto
    MUHC - McGill University Ocular Pathology Laboratory, Montreal, Quebec, Canada
  • Catherine Pancini Rezende
    MUHC - McGill University Ocular Pathology Laboratory, Montreal, Quebec, Canada
  • Christina Mastromonaco
    MUHC - McGill University Ocular Pathology Laboratory, Montreal, Quebec, Canada
  • Miguel N Burnier
    MUHC - McGill University Ocular Pathology Laboratory, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Bruna Duarte Moron de Andrade, None; Jade Lasiste, None; Denise Miyamoto, None; Catherine Pancini Rezende, None; Christina Mastromonaco, None; Miguel Burnier, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3964. doi:
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      Bruna Duarte Moron de Andrade, Jade Lasiste, Denise Miyamoto, Catherine Pancini Rezende, Christina Mastromonaco, Miguel N Burnier; Metformin inhibits survival, migration, and vascular endothelial growth factor production in uveal melanoma cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3964.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Uveal melanoma is the most common intraocular malignancy in adults. Despite advances in treatment, 50% of patients develop metastasis, 90% of which succumb to their disease. Metformin, a biguanide drug used primarily for the treatment of diabetes, has an excellent safety profile. Metformin has also been shown to reduce proliferation, metastasis and angiogenesis in a variety of tumor cells, including cutaneous melanoma. However, it has not yet been tested on uveal melanoma. The objective of this study is to determine the effect of metformin on: (1) survival, (2) migration and (3) production of the angiogenesis precursor vascular endothelial growth factor (VEGF) in the uveal melanoma cell line OCM-1.

Methods : Metformin treatment concentrations ranging from 0-100 mM were used. The cell counting kit-8 (CCK-8) viability assay was utilized to test the cytotoxicity of metformin. The scratch assay, with subsequent Image analysis, was performed to assess the effect of metformin on migration. To promote angiogenesis and test the effect of metformin on VEGF production, cells were grown in a hypoxic (1% oxygen) chamber. Secreted VEGF was quantitated using a sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis was done using Kruskal-Wallis with Dunn’s multiple comparison test for data on cytotoxicity and angiogenesis, while analysis of variance (ANOVA) with Tukey post-hoc test was used for data on migration.

Results : Metformin was lethal to half and all of the cells at 30 mM and 70 mM (LC50 and LC100, respectively). There was a significant decrease in survival (P<0.05) at 30 mM. To avoid bias due to cytotoxicity, all subsequent experiments were performed with 0-20mM metformin. Metformin significantly inhibited cell migration at 5mM metformin (P<0.05). VEGF production also decreased with the lowest dose of metformin (0.1 mM) and significantly at 5 mM (P<0.05).

Conclusions : Metformin inhibits survival, migration and production of VEGF in human uveal melanoma cells and therefore has potential as an adjunct to therapy. Studies on its mechanism of action and toxicity to proximal eye tissues should be performed. Effectiveness in in vivo models must be tested to determine the ideal dose, route and timing of administration.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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