TY - JOUR
T1 - Inhibition of epithelial-mesenchymal transition in response to treatment with metformin and Y27632 in breast cancer cell lines
AU - Leonel, Camila
AU - Ferreira, Lívia Carvalho
AU - Borin, Thaiz Ferraz
AU - Moschetta, Marina Gobbe
AU - Freitas, Gabriela Scavacini
AU - Haddad, Michel Raineri
AU - Robles, João Antonio de Camargos Pinto
AU - Zuccari, Debora Aparecida Pires de Campos
N1 - Funding Information:
This study was funded by the FAPESP/Brazil-Fundacao Amparo a Pesquisa do Estado de Sao Paulo (2012/14079-5).
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - Anticarcinogenic agents
KW - Breast cancer
KW - EMT
KW - Metformin
KW - ROCK1
KW - TGF-β
UR - http://www.scopus.com/inward/record.url?scp=85021000330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021000330&partnerID=8YFLogxK
U2 - 10.2174/1871520617666170102153954
DO - 10.2174/1871520617666170102153954
M3 - Article
C2 - 28042775
AN - SCOPUS:85021000330
SN - 1871-5206
VL - 17
SP - 1113
EP - 1125
JO - Anti-Cancer Agents in Medicinal Chemistry
JF - Anti-Cancer Agents in Medicinal Chemistry
IS - 8
ER -
