Troglitazone Inhibits Matrix Metalloproteinase-9 Expression and Invasion of Breast Cancer Cell through a Peroxisome Proliferator-Activated Receptor γ-Dependent Mechanism.
- Author:
On Yu HONG
1
;
Hyun Jo YOUN
;
Hye Yeon JANG
;
Sung Hoo JUNG
;
Eun Mi NOH
;
Hee Suk CHAE
;
Young Ju JEONG
;
Won KIM
;
Cheorl Ho KIM
;
Jong Suk KIM
Author Information
- Publication Type:Original Article
- Keywords: Matrix metalloproteinases; MCF-7 cells; NF-kappa B; PPAR gamma; Transcription factor AP-1
- MeSH: Atherosclerosis; Blotting, Western; Breast Neoplasms*; Breast*; Cell Survival; DNA; Electrophoretic Mobility Shift Assay; Gelatin; Luciferases; Matrix Metalloproteinase 9*; Matrix Metalloproteinases; MCF-7 Cells; Morphogenesis; Neoplasm Metastasis; NF-kappa B; Obesity; Pathology; Peroxisomes*; PPAR gamma; Real-Time Polymerase Chain Reaction; Transcription Factor AP-1; Transcription Factors
- From:Journal of Breast Cancer 2018;21(1):28-36
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Peroxisome proliferator-activated receptor γ (PPARγ) is involved in the pathology of numerous diseases including atherosclerosis, diabetes, obesity, and cancer. Matrix metalloproteinases (MMPs) play a significant role in tissue remodeling related to various processes such as morphogenesis, angiogenesis, tissue repair, invasion, and metastasis. We investigated the effects of PPARγ on MMP expression and invasion in breast cancer cells. METHODS: MCF-7 cells were cultured and then cell viability was monitored in an MTT assay. Western blotting, gelatin zymography, real-time polymerase chain reaction, and luciferase assays were performed to investigate the effect of the synthetic PPARγ ligand troglitazone on MMP expression. Transcription factor DNA binding was analyzed by electrophoretic mobility shift assay. A Matrigel invasion assay was used to assess the effects of troglitazone on MCF-7 cells. RESULTS: Troglitazone did not affect MCF-7 cell viability. 12-O-tetradecanoylphorbol-13-acetate (TPA) induced MMP-9 expression and invasion in MCF-7 cell. However, these effects were decreased by troglitazone. TPA increased nuclear factor κB and activator protein-1 DNA binding, while troglitazone inhibited these effects. The selective PPARγ antagonist GW9662 reversed MMP-9 inhibition by troglitazone in TPA-treated MCF-7 cells. CONCLUSION: Troglitazone inhibited nuclear factor κB and activator protein-1-mediated MMP-9 expression and invasion of MCF-7 cells through a PPARγ-dependent mechanism.
