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PPARγ activation reduces ischemia/reperfusion-induced metastasis in a murine model of hepatocellular carcinoma.

Abstract：

:Ischemia/reperfusion (I/R) injury during liver resection or transplantation for the treatment of hepatocellular carcinoma (HCC) may increase the risk of metastasis. Peroxisome proliferator-activated receptor-γ (PPARγ) activation has been observed to exert a protective effect against hepatic I/R injury. However, whether PPARγ activation exerts a protective effect against I/R-associated liver metastasis remains unknown. Therefore, the present study aimed to investigate the effects of the PPAR agonist rosiglitazone and the specific PPARγ antagonist GW9662 on tumor metastasis following hepatic I/R. An experimental mouse model of hepatic I/R-induced HCC metastasis was designed in order to determine the effects of I/R on tumor metastasis in the liver. Four groups were established: Sham, control (I/R), rosiglitazone (Ro) and rosiglitazone with GW9662 (Ro + GW) groups. In the latter two groups, the treatments were administered intravenously 1 h prior to the induction of ischemia. Tumor load was measured 12 days after the procedure. Furthermore, tissue analyses were conducted to determine the expression levels of alanine aminotransferase, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, vascular cell adhesion molecule (VCAM)-1, nuclear factor (NF)-κB and PPARγ. Rosiglitazone pretreatment appeared to significantly mitigate hepatic I/R injury, as indicated by serological and histological analysis. The levels of VCAM-1, MPO and MMP-9 expression in the Ro group were significantly reduced at 8 h following ischemia compared with those in the control and Ro + GW groups. In addition, rosiglitazone inhibited the I/R-induced activation of NF-κB, and GW9662 attenuated the inhibitory effect. To the best of our knowledge, the present study is the first to report on the expression and the functional roles of PPARγ in I/R-associated metastasis. Short-term treatment of mice with rosiglitazone, a potent PPARγ agonist, confers protective effects against hepatic I/R-associated metastasis. Thus, PPARγ may be a potential therapeutic target for the protection of the liver against I/R-associated metastasis.

journal_name

Exp Ther Med

journal_title

Experimental and therapeutic medicine

authors

Liu YI,Liu Z,Chen Y,Xu K,Dong J

doi

10.3892/etm.2015.2934

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

387-396

issue

eissn

1792-0981

issn

1792-1015

pii

ETM-0-0-2934

journal_volume

pub_type

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PPARγ activation reduces ischemia/reperfusion-induced metastasis in a murine model of hepatocellular carcinoma.