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Anticancer Agents Med Chem ; 17(8): 1113-1125, 2017.
Article in English | MEDLINE | ID: mdl-28042775

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-ß) 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-ß1 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-ß1, 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.


Subject(s)
Amides/pharmacology , Antineoplastic Agents/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Metformin/pharmacology , Pyridines/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Molecular Structure , Structure-Activity Relationship , Tumor Cells, Cultured , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/genetics , rho-Associated Kinases/metabolism
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