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. 2018 Mar 2;8:3929. doi: 10.1038/s41598-018-22054-w

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Antitumor activity of metformin gel formulation. (A) Difference of the luciferase emission (IVIS) before (day 0) and at the end of the treatment (day 21) from untreated mice (CTR), treated with placebo (Gel), or metformin-loaded gel (MH Gel). (B) Histological analysis of representative MDA MB231 tumors developed in control mice (CTR, untreated), in mice treated with metformin-loaded gel (MH Gel) or placebo (Gel). Images are representative of sections from different tumor areas, showing similar results. T = tumor area; N = necrotic area; red arrows = hemorrhagic areas and picnotic nuclei; yellow asterisks = representative mitotic cells. Bars = 50 µm. (C) Immunohistochemical analysis of representative MDA MB231 tumors developed in control mice (Ctr, untreated), in mice treated with metformin (MH)-loaded gel or placebo, stained with anti-CD31 antibody to highlight tumor vessels. Negative control (Neg) section was stained with the secondary antibody only. Bars = 100 µm.