Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits hepatoma cell growth via downregulation of SEPT2 expression

Hepatocellular carcinoma (HCC) is a malignant tumor with poor prognosis and low therapeutic efficacy. Recent studies have demonstrated the therapeutic prospect of peroxisome proliferator-activated receptor-gamma (PPAR gamma) cancer angiogenesis. However, the action mechanisms remain elusive. In the present study, by using mass spectrometry, we found that PPAR gamma ligand rosiglitazone (RGZ) could regulate HCC cell growth by influencing various downstream factors and pathways. Among the altered proteins, septin 2 (SEPT2) was found to exhibit oncogenic function. PPAR gamma overexpression could inhibit the expression of SEPT2, thus blocking the promoting effects of SEPT2 on HCC cell proliferation, invasion and its inhibitory effect on cell apoptosis. Further studies also indicated that SEPT2 promoted HCC cell growth via upregulation of matrix metalloproteinase (MMP)-2 and -9, and simultaneously inhibited the cleavage of caspase-3, -7, and -9. Interestingly, the effects of SEPT2 on the above factors could be suppressed by PPAR gamma overexpression, suggesting that PPARy gamma could inhibit HCC cell growth via regulating the expression and blocking the oncogenic function of SEPT2. Taken together, these results provide new evidence for the action mechanisms of PPAR gamma in carcinogenesis of HCC, and upon further investigation, PPAR gamma could be developed as a new target for the treatment of liver cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.