Leonel Camila, Ferreira Lívia Carvalho, Borin Thaiz Ferraz, Moschetta Marina Gobbe, Freitas Gabriela Scavacini, Haddad Michel Raineri, de Camargos Pinto Robles João Antonio, Aparecida Pires de Campos Zuccari Debora
Universidade Estadual Paulista "Julio de Mesquita Filho" (UNESP/IBILCE), Post graduate Program in Genetics, Sao Jose do Rio Preto, SP, Brazil.
Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), Laboratory of Molecular Investigation of Cancer (LIMC), Sao Jose do Rio Preto, SP, Brazil.
Anticancer Agents Med Chem. 2017;17(8):1113-1125. doi: 10.2174/1871520617666170102153954.
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.
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.
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.
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.
This study confirms the benefits of metformin and Y27632 as potential therapeutic agents in mammary tumors, by blocking EMT process and metastatic potential.
ROCK-1的表达与肿瘤的恶性特征相关，而抑制该分子可显著抑制肿瘤转移。同样，转化生长因子β（TGF-β）通过诱导上皮-间质转化（EMT）与这种恶性肿瘤相关。二甲双胍是一种用于治疗糖尿病的药物，此前已被证明可抑制乳腺癌细胞中的EMT。
本研究旨在评估TGF-β1诱导EMT的作用模型以及二甲双胍和ROCK-1抑制剂（Y27632）在乳腺癌细胞系EMT过程中的作用。
用TGF-β1诱导EMT后，用二甲双胍和Y27632处理MCF-7和MDA-MB-231细胞系，通过免疫细胞化学检测对细胞迁移以及ROCK-1标志物波形蛋白、E-钙黏蛋白、CD44和CD24蛋白表达的影响。
用二甲双胍和Y27632处理后，两种细胞系中ROCK-1、波形蛋白、CD44和CD24的蛋白表达均降低。在MDA-MB-231细胞中，所有处理组的E-钙黏蛋白表达均增加。用二甲双胍和Y27632处理MDA-MB-231细胞系显著降低了这些细胞的侵袭能力。
本研究证实了二甲双胍和Y27632作为乳腺肿瘤潜在治疗药物的益处，它们可通过阻断EMT过程和转移潜能发挥作用。
