Induction of peroxiredoxin 1 by hypoxia regulates heme oxygenase-1 via NF-κB in oral cancer.
Induction of peroxiredoxin 1 by hypoxia regulates heme oxygenase-1 via NF-κB in oral cancer.
复制标题
DOI：
10.1371/journal.pone.0105994
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tang X
中科院分区：
文献类型：
--
作者：
Zhang M;Hou M;Ge L;Miao C;Zhang J;Jing X;Shi N;Chen T;Tang X
在包括口腔鳞状细胞癌（OSCC）在内的许多癌症中观察到过氧化物酶氧还蛋白1（Prx 1）的过表达。然而，确切的分子机制的上调Prx 1的致癌作用，仍然知之甚少。本研究旨在探讨Prx 1在口腔鳞癌细胞株SCC 15和异种移植模型中与缺氧的关系及其可能的作用机制。我们处理野生型和Prx 1敲低SCC 15细胞短暂缺氧，然后复氧。检测缺氧条件、活性氧（ROS）产生、Prx 1、血红素加氧酶1（HO-1）和核因子-κ B（NF-κB）的表达和/或活性。我们发现缺氧诱导ROS积累，上调Prx 1，增加NF-κB转位和DNA结合活性，下调HO-1。在Prx 1基因敲除的细胞中，缺氧或缺氧/复氧处理后HO-1表达水平升高，NFκB转位和DNA结合活性降低。此外，我们在异种移植模型中模拟动态氧合肿瘤微环境，并分别在最大直径为2 mm、5 mm、10 mm和15 mm的肿瘤中评估上述指标。我们的数据显示肿瘤缺氧条件和Prx 1的表达与肿瘤生长显著相关。HO-1和NF-κB的表达，以及NF-κB DNA结合活性在15 mm肿瘤中显著升高，8-羟基脱氧鸟苷水平在10 mm和15 mm肿瘤中比在2 mm肿瘤中升高。本研究的结果提供了实验证据，Prx 1的过表达与缺氧有关，Prx 1/NF-κB/HO-1信号通路可能参与口腔癌的发生。
Overexpression of peroxiredoxin 1 (Prx1) has been observed in numerous cancers including oral squamous cell carcinoma (OSCC). The precise molecular mechanism of up-regulation of Prx1 in carcinogenesis, however, is still poorly understood. The objective of this study is to investigate the relationship between Prx1 and hypoxia, and potential mechanism(s) of Prx1 in OSCC cell line SCC15 and xenograft model. We treated wild-type and Prx1 knockdown SCC15 cells with transient hypoxia followed by reoxygenation. We detected the condition of hypoxia, production of reactive oxygen species (ROS), and expression and/or activity of Prx1, heme oxygenase 1 (HO-1) and nuclear factor-kappa B (NF-κB). We found that hypoxia induces ROS accumulation, up-regulates Prx1, increases NF-κB translocation and DNA binding activity, and down-regulates HO-1 in vitro. In Prx1 knockdown cells, the expression level of HO-1 was increased, while NFκB translocation and DNA binding activity were decreased after hypoxia or hypoxia/reoxygenation treatment. Moreover, we mimicked the dynamic oxygenation tumor microenvironment in xenograft model and assessed the above indices in tumors with the maximal diameter of 2 mm, 5 mm, 10 mm or 15 mm, respectively. Our data showed that tumor hypoxic condition and expression of Prx1 are significantly associated with tumor growth. The expression of HO-1 and NF-κB, and NF-κB DNA binding activity were significantly elevated in 15 mm tumors, and the level of 8-hydroxydeoxyguanosine was increased in 10 mm and 15 mm tumors, compared to those in size of 2 mm. The results from this study provide experimental evidence that overexpression of Prx1 is associated with hypoxia, and Prx1/NF-κB/HO-1 signaling pathway may be involved in oral carcinogenesis.
登录
查看更多内容
影响因子：
3.7
作者：
Riddell JR;Maier P;Sass SN;Moser MT;Foster BA;Gollnick SO
通讯作者：
Gollnick SO
DOI：
10.1016/j.mrgentox.2008.09.021
发表时间：
2009-03-31
影响因子：
1.9
作者：
Ruiz-Ramos, Ruben;Lopez-Carrillo, Lizbeth;Cebrian, Mariano E.
通讯作者：
Cebrian, Mariano E.
影响因子：
7.4
作者：
Hansen, Jason M.;Moriarty-Craige, Siobhan;Jones, Dean P.
通讯作者：
Jones, Dean P.
影响因子：
11.2
作者：
Riddell JR;Bshara W;Moser MT;Spernyak JA;Foster BA;Gollnick SO
通讯作者：
Gollnick SO
影响因子：
3.6
作者：
Allan, Marcus E.;Storey, Kenneth B.
通讯作者：
Storey, Kenneth B.