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Oncotarget：靶向铁代谢为逆转卵巢癌耐药性提供新策略

2017-08-04 Emma MedSci原创

卵巢癌顺铂耐药铁代谢
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Nrf2的诱导作用参与卵巢癌的顺铂耐药。SLC40A1（溶质载体家族40成员1）与铁浓度密切相关，研究提示其具有许多可能的Nrf2结合位点。

Nrf2的诱导作用参与卵巢癌的顺铂耐药。SLC40A1（溶质载体家族40成员1）与铁浓度密切相关，研究提示其具有许多可能的Nrf2结合位点。研究人员推测SLC40A1是Nrf2的一个可能的下游基因，探究了其在卵巢癌细胞中的作用。研究结果首次证明Nrf2可以抑制SLC40A1的转录表达，SLC40A1引起的铁过载导致卵巢癌顺铂耐药，靶向铁代谢可能是逆转卵巢癌治疗耐药性的新治疗策略。

与顺铂敏感型卵巢癌细胞相比，顺铂耐药型卵巢癌细胞Nrf2水平升高，SLC40A1水平降低。Nrf2的外源性敲低导致SLC40A1的表达增加，Nrf2的过度表达导致SLC40A1的表达降低。染色质免疫沉淀（ChIP）和双荧光素酶报告基因分析显示Nrf2抑制SLC40A1的转录。SLC40A1的过表达能够逆转Nrf2诱导的顺铂耐药性，而SLC40A1的敲低可以恢复顺铂耐药性，并提高铁浓度。此外，铁离子螯合剂去铁胺能够通过铁剥夺克服顺铂耐药，并且当其与brusatol（Nrf2抑制剂）联合治疗时，该功能得到提升。

原始出处：

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    2018-01-12 仁医06

    #target#

    0

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    2017-08-06 12498568m52暂无昵称

    #新策略#

    0

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    2017-08-06 syscxl

    #铁代谢#

    0

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    2017-08-05 flysky120

    希望能够治疗癌症

    0

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    2017-08-05 1e10c84am36(暂无匿称)

    文章真好，赞赞赞

    0

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    2017-08-05 刘煜

    学习了谢谢分享

    0

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    2017-08-05 jihuaijun1112

    学习学习学习

    0

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