Estrogen suppresses hepatocellular carcinoma cells through ERβ-mediated upregulation of the NLRP3 inflammasome
Estrogen suppresses hepatocellular carcinoma cells through ERβ-mediated upregulation of the NLRP3 inflammasome
复制标题
雌激素通过 ER beta 介导的 NLRP3 炎症小体上调抑制肝细胞癌细胞
DOI：
10.1038/labinvest.2015.63
复制
发表时间：
2015-07-01
影响因子：
5
通讯作者：
Han, Lihui
中科院分区：
文献类型：
--
作者：
Wei, Qing;Guo, Pengbo;Han, Lihui
肝细胞癌（HCC）是世界范围内最常见的恶性肿瘤之一。男性HCC的发病率明显高于女性。显著的性别差异表明性激素在HCC发病中的重要作用。近年来，雌激素在肝癌的发生、发展中起保护作用，但雌激素是否能预防和减轻肝癌的发生、发展及其保护作用机制尚未阐明。本研究显示，与正常肝组织相比，雌激素受体（ER）β在肝癌组织中的表达显著下调;而且，其表达水平与疾病进展呈显著负相关，与NLRP 3炎性体组分的表达水平呈正相关。在先前的研究中，我们发现HCC组织中NLRP 3炎性体的丢失有助于肿瘤进展，而其失调的机制尚未阐明。在这项研究中，我们研究了NLRP 3炎性小体和雌激素之间的潜在联系。我们的数据显示，17 β-雌二醇（E2）治疗显着抑制肝癌细胞的恶性行为，通过E2/ER β/MAPK途径介导的NLRP 3炎性体的上调。这项研究显示了ER β和NLRP 3炎性小体在HCC进展中的新联系，这为HCC患者的治疗提供了一种潜在的有价值的治疗策略。
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The incidence of HCC is strikingly higher in males than in females. The remarkable gender disparity suggests an important role for sex hormones in HCC pathogenesis. Recently, estrogen has emerged as a protective factor in the development and progression of HCC, but whether it prevents and attenuates HCC, and the mechanism of protection, have not been elucidated. The present study shows that expression of estrogen receptor (ER) beta was significantly downregulated in HCC tissue compared with normal liver tissue; moreover, its expression level showed a significant negative correlation with disease progression and a positive correlation with the expression level of NLRP3 inflammasome components. In a previous study, we showed that loss of NLRP3 inflammasome in HCC tissue contributed to tumor progression, whereas the mechanism of its deregulation was not elucidated. In this study, we investigated the potential link between NLRP3 inflammasome and estrogen. Our data reveal that treatment with 17 beta-estradiol (E2) significantly inhibited the malignant behavior of HCC cells through E2/ER beta/MAPK pathway-mediated upregulation of the NLRP3 inflammasome. This study shows a novel link between ER beta and the NLRP3 inflammasome in HCC progression, which provides a potentially valuable therapeutic strategy for treatment of HCC patients.