Evaluation of angiogenesis process after metformin and LY294002 treatment in mammary tumor

Marina G. Moschetta, Camila Leonel, Larissa B. Maschio-Signorini, Thaiz F. Borin, Gabriela B. Gelaleti, Bruna V. Jardim-Perassi, Lívia C. Ferreira, Nathália M. Sonehara, Livia G.S. Carvalho, Eva Hellmén, Debora A.P.de Campos Zuccari

Research output: Contribution to journalArticle

1 Scopus citations


Background: The angiogenesis process is regulated by many factors, such as Hypoxia-Inducible Factor-1 (HIF-1) and Vascular Endothelial Growth Factor (VEGF). Metformin has demonstrated its ability to inhibit cell growth and the LY294002 is the major inhibitor of PI3K/AKT/mTOR pathway that has antiangiogenic properties. Methods: Canine mammary tumor cell lines CMT-U229 and CF41 were treated with metformin and LY294002. Cell viability, protein and gene expression of VEGF and HIF-1 were determined in vitro. For the in vivo study, CF41 cells were inoculated in female athymic nude mice treated with either metformin or LY294002. The mi-crovessel density by immunohistochemistry for CD31 as well as the gene and protein expression of HIF-1 and VEGF were evaluated. Results: The treatment with metformin and LY294002 was able to reduce the cellular viability after 24 hours. The protein and gene expression of HIF-1 and VEGF decreased after treatment with metformin and LY294002. In the in vivo study, there was a decrease in tumor size, protein and gene expression of HIF-1 and VEGFA, in addition to the decreasing of CD31 expression after all treatments. Conclusion: Our results demonstrate the effectiveness of metformin and LY294002 in controlling the angiogenesis process in mammary tumors by VEGF and HIF-1, the most important angiogenic markers.

Original languageEnglish (US)
Pages (from-to)655-666
Number of pages12
JournalAnti-Cancer Agents in Medicinal Chemistry
Issue number5
StatePublished - Jan 1 2019


  • Angiogenesis
  • Canine mammary tumors
  • Hypoxia
  • Hypoxia-inducible factor-1α
  • Mammary tumors
  • Metformin
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Cancer Research

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  • Cite this

    Moschetta, M. G., Leonel, C., Maschio-Signorini, L. B., Borin, T. F., Gelaleti, G. B., Jardim-Perassi, B. V., Ferreira, L. C., Sonehara, N. M., Carvalho, L. G. S., Hellmén, E., & Zuccari, D. A. P. D. C. (2019). Evaluation of angiogenesis process after metformin and LY294002 treatment in mammary tumor. Anti-Cancer Agents in Medicinal Chemistry, 19(5), 655-666. https://doi.org/10.2174/1871520619666181218164050