Activation of PPAR eta suppresses proliferation and induces apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway

作者：Wu, Kai; Yang, Yang; Liu, Donglei; Qi, Yu; Zhang, Chunyang; Zhao, Jia; Zhao, Song^*

来源：Oncotarget, 2016, 7(28): 44572-44582.

DOI：10.18632/oncotarget.10067

• PPAR
• MAPK pathway
• TLR4
• esophageal cancer

Although substantial studies on peroxisome proliferator-activated receptor eta (PPAR eta) have focused on the mechanisms by which PPAR eta regulates glucose and lipid metabolism, recent reports have suggested that PPAR eta shows tumorigenic or antitumorigenic effects. The roles and mechanisms of PPAR eta activation in esophageal cancer remain unclarified. EC109 and TE10 esophageal cancer cells were treated with 0, 10, 20 and 40 mM of PPAR eta agonist rosiglitazone (RGZ) for 24, 48, and 72 h, and the cell viability and apoptosis were detected using methyl thiazolyl tetrazolium (MTT) assay and Flow cytometric (FCM) analysis, respectively. Moreover, the effects of inhibition of PPAR eta by antagonist or specific RNA interference on cell viability, apoptosis, the Toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK) pathways were evaluated. Additionally, the effect of TLR4 signaling on the MAPK pathway, cell viability and apoptosis was assessed. The results showed that RGZ suppressed proliferation and induced apoptosis of esophageal cancer cells, which could be partly restored by inactivation of PPAR eta. RGZ suppressed the MAPK and TLR4 pathways, and the inhibitory effect could be counteracted by PPAR eta antagonist or specific RNA interference. We also suggested that MAPK activation was regulated by the TLR4 pathway and that blocking the TLR4 and MAPK pathways significantly suppressed proliferation and induced apoptosis of esophageal cancer cells. In conclusion, our data suggested that activation of PPAR eta suppressed proliferation and induced apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway.

• 出版日期2016-7-12
• 单位郑州大学