Evaluation of Angiogenesis Process after Metformin and LY294002 Treatment in Mammary Tumor

Autor(es):Mostrar menos -

Moschetta, Marina G. ^[1] ; Leonel, Camila ^[1] ; Maschio-Signorini, Larissa B. ^[1] ; Borin, Thaiz F. ^[2] ; Gelaleti, Gabriela B. ^[1] ; Jardim-Perassi, Bruna V. ^[3] ; Ferreira, Livia C. ^[1] ; Sonehara, Nathalia M. ^[1] ; Carvalho, Livia G. S. ^[1] ; Hellmen, Eva ^[4] ; de Campos Zuccari, Debora A. P. ^[1]

Afiliação do(s) autor(es)

^[1] Fac Med Sao Jose Do Rio Preto FAMERP, Dept Mol Biol, LIMC, Sao Jose Do Rio Preto, SP - Brazil

^[2] Augusta Univ, Dept Biochem & Mol Biol, Tumor Imaging Angiogenesis Lab, Augusta, GA - USA

^[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL - USA

^[4] Swedish Univ Agr Sci SLU, Dept Anat Physiol & Biochem, Uppsala - Sweden

• Tipo de documento: Artigo Científico
• Fonte: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 19, n. 5, p. 655-666, 2019.
• Citações Web of Science: 0

Resumo

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 microvessel 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. (AU)

• Processo FAPESP: 13/19862-2 - BLOQUEIO SIMULTÂNEO DA ANGIOGÊNESE PELAS VIAS DE SINALIZAÇÃO PI3K E MAPK/AKT/mTOR APÓS TRATAMENTO COM METFORMINA E LY294002 NO CÂNCER DE MAMA
• Beneficiário: Marina Gobbe Moschetta
• Modalidade de apoio: Bolsas no Brasil - Doutorado