TY - JOUR
T1 - Evaluation of angiogenesis process after metformin and LY294002 treatment in mammary tumor
AU - Moschetta, Marina G.
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
N1 - Funding Information:
We thank Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (grants #2012/14079-6, #2013/19862-2) and Fun-dação de Apoio à Pesquisa e Extensão de São José do Rio Preto - FAPERP (grant #091/2014) which funded this research.
Publisher Copyright:
© 2019 Bentham Science Publishers.
PY - 2019
Y1 - 2019
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.
KW - Angiogenesis
KW - Canine mammary tumors
KW - Hypoxia
KW - Hypoxia-inducible factor-1α
KW - Mammary tumors
KW - Metformin
KW - Vascular endothelial growth factor
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U2 - 10.2174/1871520619666181218164050
DO - 10.2174/1871520619666181218164050
M3 - Article
C2 - 30569877
AN - SCOPUS:85071018244
SN - 1871-5206
VL - 19
SP - 655
EP - 666
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
IS - 5
ER -
