Flumethasone enhances the efficacy of chemotherapeutic drugs in lung cancer by inhibiting Nrf2 signaling pathway.
Flumethasone enhances the efficacy of chemotherapeutic drugs in lung cancer by inhibiting Nrf2 signaling pathway.
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氟米松通过抑制Nrf2信号通路增强化疗药物对肺癌的疗效。
DOI：
10.1016/j.canlet.2020.01.010
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发表时间：
2020-01
期刊：
影响因子：
9.7
通讯作者：
Hu Rong
中科院分区：
文献类型：
--
作者：
Zhou Yunjiang;Zhou Yang;Wang Keke;Li Tao;Yang Mengdi;Wang Rui;Chen Yaxin;Cao Mengran;Hu Rong
核因子红细胞 2 相关因子 2 (Nrf2) 是一种转录因子，通过调节细胞保护和抗氧化基因的表达，参与保护细胞免受亲电或氧化应激。它已成为癌症化疗增敏的新兴靶点之一，Nrf2的小分子抑制剂可以增强化疗药物的疗效。在这里，我们发现氟米松（一种糖皮质激素）通过促进 Nrf2 蛋白降解来抑制 A549 和 H460 细胞中的 Nrf2 信号传导。此外，氟米松显着增加了 A549 和 H460 细胞对顺铂、阿霉素和 5-FU 等化疗药物的敏感性。在携带A549-shControl细胞来源的异种移植物的小鼠中，氟米松和顺铂联合组的异种移植物的大小和重量与顺铂组相比显着减少，而在携带A549-shNrf2细胞来源的异种移植物的小鼠中，联合组的异种移植物的大小和重量与对照组相比没有显着差异。 顺铂组，证明氟米松的化疗增敏作用是Nrf2依赖性的。这项工作表明氟米松有可能用作辅助增敏剂，以增强肺癌化疗药物的疗效。
Nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor, participates in protecting cells from electrophilic or oxidative stresses through regulating expression of cytoprotective and antioxidant genes. It has become one of the emerging targets for cancer chemosensitization, and small molecule inhibitors of Nrf2 can enhance the efficacy of chemotherapeutic drugs. Here, we found that flumethasone, a glucocorticoid, inhibited Nrf2 signaling in A549 and H460 cells by promoting Nrf2 protein degradation. Moreover, flumethasone significantly increased the sensitivity of A549 and H460 cells to chemotherapeutic drugs including cisplatin, doxorubicin and 5-FU. In mice bearing A549-shControl cells-derived xenografts, the size and weight of xenografts in the flumethasone and cisplatin combination group had a significant reduction compared with those in the cisplatin group, while in mice bearing A549-shNrf2 cells-derived xenografts, the size and weight of the xenografts in the combination group had no significant difference compared with those in the cisplatin group, demonstrating that chemosensitization effect of flumethasone is Nrf2-dependent. This work suggests that flumethasone can potentially be used as an adjuvant sensitizer to enhance the efficacy of chemotherapeutic drugs in lung cancer.
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影响因子：
5.3
作者：
Zhang, DD;Lo, SC;Hannink, M
通讯作者：
Hannink, M
影响因子：
11.5
作者：
Homma, Shinsuke;Ishii, Yukio;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki
影响因子：
2.9
作者：
Hong YB;Kang HJ;Kwon SY;Kim HJ;Kwon KY;Cho CH;Lee JM;Kallakury BV;Bae I
通讯作者：
Bae I
DOI：
10.1158/1078-0432.ccr-09-3352
发表时间：
2010-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Solis LM;Behrens C;Dong W;Suraokar M;Ozburn NC;Moran CA;Corvalan AH;Biswal S;Swisher SG;Bekele BN;Minna JD;Stewart DJ;Wistuba II
通讯作者：
Wistuba II
喜树碱抑制 NRF2-ARE 活性并使肝细胞癌细胞对抗癌药物敏感
影响因子：
8.8
作者：
Chen F;Wang H;Zhu J;Zhao R;Xue P;Zhang Q;Bud Nelson M;Qu W;Feng B;Pi J
通讯作者：
Pi J