Estrogen-related receptor alpha confers methotrexate resistance via attenuation of reactive oxygen species production and P53 mediated apoptosis in osteosarcoma cells.
机构：[1]First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China深圳市中医院深圳医学信息中心[2]Cancer Center, University of California, Davis, Sacramento, CA 95817, USA[3]State Key Hip Joints Center, First Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 12 Jichang Road, Guangzhou, Guangdong 510405, China深圳市中医院深圳医学信息中心
Osteosarcoma (OS) is a malignant tumor mainly occurring in children and adolescents. Methotrexate (MTX), a chemotherapy agent, is widely used in treating OS. However, treatment failures are common due to acquired chemoresistance, for which the underlying molecular mechanisms are still unclear. In this study, we report that overexpression of estrogen-related receptor alpha (ERR α ), an orphan nuclear receptor, promoted cell survival and blocked MTX-induced cell death in U2OS cells. We showed that MTX induced ROS production in MTX-sensitive U2OS cells while ERR α effectively blocked the ROS production and ROS associated cell apoptosis. Our further studies demonstrated that ERR α suppressed ROS induction of tumor suppressor P53 and its target genes NOXA and XAF1 which are mediators of P53-dependent apoptosis. In conclusion, this study demonstrated that ERR α plays an important role in the development of MTX resistance through blocking MTX-induced ROS production and attenuating the activation of p53 mediated apoptosis signaling pathway, and points to ERR α as a novel target for improving osteosarcoma therapy.
基金：
an NIH Grant R01DK060019 to
Hongwu Chen and the National Nature Science Foundation
of China (nos. 81373655 and 81173284).
语种：
外文
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出版当年[2013]版：
无
最新[2025]版：
大类|4 区医学
小类|4 区生物工程与应用微生物4 区医学：研究与实验
第一作者：
第一作者机构：[1]First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China[2]Cancer Center, University of California, Davis, Sacramento, CA 95817, USA
共同第一作者：
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推荐引用方式(GB/T 7714)：
Chen Peng,Wang Haibin,Duan Zhijian,et al.Estrogen-related receptor alpha confers methotrexate resistance via attenuation of reactive oxygen species production and P53 mediated apoptosis in osteosarcoma cells.[J].BioMed research international.2014,2014:616025.doi:10.1155/2014/616025.
APA：
Chen Peng,Wang Haibin,Duan Zhijian,Zou June X,Chen Hongwu...&Wang Junjian.(2014).Estrogen-related receptor alpha confers methotrexate resistance via attenuation of reactive oxygen species production and P53 mediated apoptosis in osteosarcoma cells..BioMed research international,2014,
MLA：
Chen Peng,et al."Estrogen-related receptor alpha confers methotrexate resistance via attenuation of reactive oxygen species production and P53 mediated apoptosis in osteosarcoma cells.".BioMed research international 2014.(2014):616025
