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

[ Vol. 17 , Issue. 8 ]

Author(s):

Camila Leonel, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Marina Gobbe Moschetta, Gabriela Scavacini Freitas, Michel Raineri Haddad, João Antonio de Camargos Pinto Robles and Debora Aparecida Pires de Campos Zuccari   Pages 1113 - 1125 ( 13 )

Abstract:


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-β) 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-β1 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-β1, 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.

Keywords:

Breast cancer, anticarcinogenic agents, TGF-β, EMT, ROCK1, metformin.

Affiliation:

Universidade Estadual Paulista “Julio de Mesquita Filho” (UNESP/IBILCE), Post graduate Program in Genetics, Sao Jose do Rio Preto, SP, Universidade Estadual Paulista “Julio de Mesquita Filho” (UNESP/IBILCE), Post graduate Program in Genetics, Sao Jose do Rio Preto, SP, Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Laboratory of Molecular Investigation of Cancer (LIMC), Sao Jose do Rio Preto, SP, Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Post graduate Program in Health Science, Sao Jose do Rio Preto, SP, Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Laboratory of Molecular Investigation of Cancer (LIMC), Sao Jose do Rio Preto, SP, Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Laboratory of Molecular Investigation of Cancer (LIMC), Sao Jose do Rio Preto, SP, Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Laboratory of Molecular Investigation of Cancer (LIMC), Sao Jose do Rio Preto, SP, Laboratory of Molecular Investigation of Cancer (LIMC), FAMERP – Faculdade de Medicina de Sao Jose do Rio Preto, Av. Brigadeiro Faria Lima 5416, 15090.000 Sao Jose do Rio Preto, Sao Paulo, Brazil

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