RESUMO
Triple-negative breast cancer (TNBC) is characterized by great metastasis and invasion capability. Our study revealed that nanomolar bisphenol A (BPA), one of the most ubiquitous endocrine disruptors, can increase wound closure and invasion of both MDA-MB-231 and BT-549 cells. BPA treatment can increase protein and mRNA expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, while had no effect on the expression of vimentin (Vim) and fibronectin (FN) in TNBC cells. The expression of G-protein-coupled receptor (GPER), which has been suggested to mediate rapid oestrogenic signals, was not varied in BPA-treated MDA-MB-231 and BT-549 cells. Its inhibitor G15 also had no effect on BPA-induced MMPs expression and cell invasion. Interestingly, BPA treatment can significantly increase the mRNA and protein expressions of oestrogen-related receptor γ (ERRγ), but not ERRα or ERRß, in both MDA-MB-231 and BT-549 cells. The knock-down of ERRγ can markedly attenuate BPA-induced expression of MMP-2 and MMP-9 in TNBC cells. BPA treatment can activate both ERK1/2 and Akt in TNBC cells. Both inhibitors of ERK1/2 (PD98059) and Akt (LY294002) can attenuate BPA-induced ERRγ expression and cell invasion of MDA-MB-231 cells. Collectively, our data revealed that BPA can increase the expression of MMPs and in vitro motility of TNBC cells via ERRγ. Both activation of ERK1/2 and Akt participated in this process. Our study suggests that more attention should be paid to the roles of xenoestrogens such as BPA in the development and progression of TNBC.
Assuntos
Compostos Benzidrílicos/toxicidade , Carcinógenos Ambientais/toxicidade , Disruptores Endócrinos/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Fenóis/toxicidade , Receptores de Estrogênio/metabolismo , Neoplasias de Mama Triplo Negativas/induzido quimicamente , Compostos Benzidrílicos/antagonistas & inibidores , Carcinógenos Ambientais/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Disruptores Endócrinos/química , Indução Enzimática/efeitos dos fármacos , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/química , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Concentração Osmolar , Fenóis/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/agonistas , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Mensageiro/metabolismo , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/química , Receptores de Estrogênio/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
OBJECTIVE: To investigate the effect of Aloe emodin (AE) on the invasive and metastatic abilities of human high metastatic breast cancer MDA-MB-231 cells. METHODS: MTT assay was used to evaluate the viability of MDA-MB-231 cells after treated with AE for 6 h and 24 h. The adhesive potential of MDA-MB-231 cells to FN and LN was tested by cell-matrix adhesion assay. The effect of AE on invasion of MDA-MB-231 cells was measured by Transwell chamber assay. Scratch wound healing assay was applied to determine the effect on migration of MDA-MB-231 cells. The effect of AE on MDA-MB-231 lung metastasis was determined on an experimental metastatic model. RESULTS: 80 micromol/L AE significantly inhibited the invasion, adhesion to FN, LN of MDA-MB-231 cells in vitro, the inhibitory rates were (52.98 +/- 5.46)%, (34.99 +/- 2.63)%, (28.73 +/- 7.00)%, respectively. After 24 h treatment, AE significantly inhibited the migration of MDA-MB-231 cells. The number and volume of lung metastatic nodules formed by MDA-MB-231 cells after 80 micromol/L AE 24 h treatment were decreased compared with control group. CONCLUSION: AE can suppress the metastasis of MDA-MB-231 cells. Their mechanisms may be related to the inhibition of the capabilities of invasion and migration of MDA-MB-231 cells.