Open AccessPeroxisome proliferator‐activated receptor‐γ activation inhibits hepatocellular carcinoma cell invasion by upregulating plasminogen activator inhibitor‐1
Author(s) -
Pang Xiaojuan,
Wei Yinna,
Zhang Ya,
Zhang Minyue,
Lu Yan,
Shen Pingping
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12143
Subject(s) - peroxisome proliferator activated receptor , cancer research , downregulation and upregulation , cell growth , biology , cell , receptor , transcription factor , cell culture , nuclear receptor , apoptosis , peroxisome proliferator activated receptor alpha , gene knockdown , microbiology and biotechnology , biochemistry , genetics , gene
The peroxisome proliferator‐activated receptor‐γ ( PPAR γ) is a ligand‐activated transcription factor belonging to the nuclear receptor superfamily. Peroxisome proliferator‐activated receptor‐γ ligands can inhibit cell growth and increase apoptosis of cancer cell lines, suggesting a potential role for PPAR γ as a tumor suppressor. Whereas the related studies between PPAR γ and cancer cell invasion are still poor. Our previous study indicates that β‐estradiol (E2) suppresses hepatocellular carcinoma ( HCC ) cell invasion. We report here that E2 can activate PPAR γ of HCC cells, and activated PPAR γ suppresses cell invasion by upregulating the expression level of plasminogen activator inhibitor‐1 ( PAI ‐1). We found that PPAR γ plays an important role in the E2‐induced HCC cell invasion process. Using PPAR γ agonist GW 1929, a reduced invasion effect was found in HCC cell lines, and this inhibition of cell invasion was dosage‐dependent. However, cell invasion was restored by treatment with PPAR γ antagonist GW 9662. The activated PPAR γ upregulated the expression of cell migration‐related protein PAI ‐1. Furthermore, knockdown of PPAR γ in HCC cells decreased the level of PAI ‐1 and advanced cell invasion in response to GW 1929. On the contrary, overexpression of PPAR γ in HCC cells elevated the level of PAI ‐1 and inhibited cell invasion. These findings suggest that PPAR γ activation inhibits HCC cell invasion via the upregulation of PAI ‐1 and implicate that PPAR γ is a target for the treatment and prevention of HCC cell invasion.