KMID : 1134120180210010028
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Journal of Breast Cancer 2018 Volume.21 No. 1 p.28 ~ p.36
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Troglitazone Inhibits Matrix Metalloproteinase-9 Expression and Invasion of Breast Cancer Cell through a Peroxisome Proliferator-Activated Receptor ¥ã-Dependent Mechanism
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Hong On-Yu
Youn Hyun-Jo Jang Hye-Yeon Jung Sung-Hoo Noh Eun-Mi Chae Hee-Suk Jeong Young-Ju Kim Won Kim Cheorl-Ho Kim Jong-Suk
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Abstract
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Purpose: Peroxisome proliferator-activated receptor ¥ã (PPAR¥ã) 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 PPAR¥ã 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 PPAR¥ã 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 ¥êB and activator protein-1 DNA binding, while troglitazone inhibited these effects. The selective PPAR¥ã antagonist GW9662 reversed MMP-9 inhibition by troglitazone in TPA-treated MCF-7 cells.
Conclusion: Troglitazone inhibited nuclear factor ¥êB and activator protein-1-mediated MMP-9 expression and invasion of MCF-7 cells through a PPAR¥ã-dependent mechanism.
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KEYWORD
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Matrix metalloproteinases, MCF-7 cells, NF-kappa B, PPAR gamma, Transcription factor AP-1
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