Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines

Autor(es)

Leonel, Camila ; Ferreira, Livia Carvalho ; Borin, Thaiz Ferraz ; Moschetta, Marina Gobbe ; Freitas, Gabriela Scavacini ; Haddad, Michel Raineri ; de Camargos Pinto Robles, Joao Antonio ; Pires de Campos Zuccari, Debora Aparecida

• Tipo de documento: Artigo Científico
• Fonte: ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY; v. 17, n. 8, p. 1113-1125, 2017.
• Citações Web of Science: 5

Resumo

Background: ROCK-1 expression is associated with the malignant character of tumors, while inhibiting this molecule results in a significant suppression of tumor metastasis. Likewise, transforming growth factor beta (TGF-beta) is associated with this malignancy by having the ability to induce epithelial-mesenchymal transition (EMT). Metformin, a drug used in the treatment of diabetes, has previously been shown to inhibit EMT in breast cancer cells. Objective: The aim of this study is to evaluate the TGF-beta 1 action model for induction of EMT and the action of metformin and ROCK-1 inhibitor (Y27632) in EMT process in breast cancer cell lines. Method: MCF-7 and MDA-MB-231 cell lines were treated with metformin and Y27632, after induction of EMT by TGF-beta 1, to examine the effects on cell migration as well as the protein expression of the ROCK-1 markers, vimentin, E-cadherin, CD44 and CD24 by immunocitochemistry. Results: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632. In MDA-MB-231 cells, E-cadherin expression was increased in all treatment groups. Treatment of MDA-MB-231 cell line with metformin and Y27632 significantly reduced the invasion of these cells. Conclusion: This study confirms the benefits of metformin and Y27632 as potential therapeutic agents in mammary tumors, by blocking EMT process and metastatic potential. (AU)

• Processo FAPESP: 12/14079-5 - Inibição da metástase via transição epitélio-mesenquimal por RNA de interferência e metformina em neoplasia mamária
• Beneficiário: Debora Aparecida Pires de Campos Zuccari
• Modalidade de apoio: Auxílio à Pesquisa - Regular