Wu Kai, Yang Yang, Liu Donglei, Qi Yu, Zhang Chunyang, Zhao Jia, Zhao Song
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Oncotarget. 2016 Jul 12;7(28):44572-44582. doi: 10.18632/oncotarget.10067.
Although substantial studies on peroxisome proliferator-activated receptor g (PPARg) have focused on the mechanisms by which PPARg regulates glucose and lipid metabolism, recent reports have suggested that PPARg shows tumorigenic or antitumorigenic effects. The roles and mechanisms of PPARg activation in esophageal cancer remain unclarified. EC109 and TE10 esophageal cancer cells were treated with 0, 10, 20 and 40 mM of PPARg 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 PPARg 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 PPARg. RGZ suppressed the MAPK and TLR4 pathways, and the inhibitory effect could be counteracted by PPARg 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 PPARg suppressed proliferation and induced apoptosis of esophageal cancer cells by inhibiting TLR4-dependent MAPK pathway.
尽管关于过氧化物酶体增殖物激活受体γ（PPARγ）的大量研究聚焦于PPARγ调节葡萄糖和脂质代谢的机制，但最近的报道表明PPARγ具有致瘤或抗肿瘤作用。PPARγ激活在食管癌中的作用和机制仍不明确。用0、10、20和40 mM的PPARγ激动剂罗格列酮（RGZ）处理EC109和TE10食管癌细胞24、48和72小时，分别使用甲基噻唑基四氮唑（MTT）法和流式细胞术（FCM）分析检测细胞活力和凋亡情况。此外，评估了拮抗剂或特异性RNA干扰抑制PPARγ对细胞活力、凋亡、Toll样受体4（TLR4）和丝裂原活化蛋白激酶（MAPK）途径的影响。另外，评估了TLR4信号对MAPK途径、细胞活力和凋亡的影响。结果表明，RGZ抑制食管癌细胞增殖并诱导其凋亡，PPARγ失活可部分恢复这种作用。RGZ抑制MAPK和TLR4途径，PPARγ拮抗剂或特异性RNA干扰可抵消这种抑制作用。我们还表明，MAPK激活受TLR4途径调节，阻断TLR4和MAPK途径可显著抑制食管癌细胞增殖并诱导其凋亡。总之，我们的数据表明，PPARγ激活通过抑制TLR4依赖性MAPK途径抑制食管癌细胞增殖并诱导其凋亡。
