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.
Anti-Cancer Agents in Medicinal Chemistry
Title:Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines
Volume: 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*
Affiliation:
- 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,Brazil
Keywords: Breast cancer, anticarcinogenic agents, TGF-β, EMT, ROCK1, metformin.
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.Export Options
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Cite this article as:
Leonel Camila, Ferreira Carvalho Lívia, Borin Ferraz Thaiz, Moschetta Gobbe Marina, Freitas Scavacini Gabriela, Haddad Raineri Michel, de Camargos Pinto Robles Antonio João and Aparecida Pires de Campos Zuccari Debora*, Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (8) . https://dx.doi.org/10.2174/1871520617666170102153954
DOI https://dx.doi.org/10.2174/1871520617666170102153954 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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