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

Abstract

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
Volume19
Issue number5
DOIs
StatePublished - Jan 1 2019

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Hypoxia-Inducible Factor 1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Metformin
Vascular Endothelial Growth Factor A
Breast Neoplasms
Gene Expression
Nude Mice
Proteins
Therapeutics
Tumor Cell Line
Phosphatidylinositol 3-Kinases
Canidae
Cell Survival
Immunohistochemistry
Growth
Neoplasms

Keywords

  • 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

Cite this

Moschetta, M. G., Leonel, C., Maschio-Signorini, L. B., Borin, T. F., Gelaleti, G. B., Jardim-Perassi, B. V., ... 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

Evaluation of angiogenesis process after metformin and LY294002 treatment in mammary tumor. / Moschetta, Marina G.; Leonel, Camila; Maschio-Signorini, Larissa B.; Borin, Thaiz F.; Gelaleti, Gabriela B.; Jardim-Perassi, Bruna V.; Ferreira, Lívia C.; Sonehara, Nathália M.; Carvalho, Livia G.S.; Hellmén, Eva; Zuccari, Debora A.P.de Campos.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 19, No. 5, 01.01.2019, p. 655-666.

Research output: Contribution to journalArticle

Moschetta, MG, Leonel, C, Maschio-Signorini, LB, Borin, TF, Gelaleti, GB, Jardim-Perassi, BV, Ferreira, LC, Sonehara, NM, Carvalho, LGS, Hellmén, E & Zuccari, DAPDC 2019, 'Evaluation of angiogenesis process after metformin and LY294002 treatment in mammary tumor', Anti-Cancer Agents in Medicinal Chemistry, vol. 19, no. 5, pp. 655-666. https://doi.org/10.2174/1871520619666181218164050
Moschetta, Marina G. ; Leonel, Camila ; Maschio-Signorini, Larissa B. ; Borin, Thaiz F. ; Gelaleti, Gabriela B. ; Jardim-Perassi, Bruna V. ; Ferreira, Lívia C. ; Sonehara, Nathália M. ; Carvalho, Livia G.S. ; Hellmén, Eva ; Zuccari, Debora A.P.de Campos. / Evaluation of angiogenesis process after metformin and LY294002 treatment in mammary tumor. In: Anti-Cancer Agents in Medicinal Chemistry. 2019 ; Vol. 19, No. 5. pp. 655-666.
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abstract = "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.",
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AU - Leonel, Camila

AU - Maschio-Signorini, Larissa B.

AU - Borin, Thaiz F.

AU - Gelaleti, Gabriela B.

AU - Jardim-Perassi, Bruna V.

AU - Ferreira, Lívia C.

AU - Sonehara, Nathália M.

AU - Carvalho, Livia G.S.

AU - Hellmén, Eva

AU - Zuccari, Debora A.P.de Campos

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N2 - 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.

AB - 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.

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