15d-PGJ2 inhibits NF-?B and AP-1-mediated MMP-9 expression and invasion of breast cancer cell by means of a heme oxygenase-1-dependent mechanism.
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ABSTRACT: Activation of peroxisome proliferator-activated receptor ? (PPAR?) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and overexpressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPAR?. In this study, we investigated the effects of induction of HO-1 by PPAR? on TPAinduced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-?B /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPAR? ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP- 9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPAR?/HO-1 signaling- pathway inhibition may be beneficial for prevention and treatment of breast cancer. [BMB Reports 2020; 53(4): 212-217].
PROVIDER: S-EPMC7196191 | BioStudies |
REPOSITORIES: biostudies
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