Ferroptosis: A Novel Anti-tumor Action for Cisplatin.
Ferroptosis: A Novel Anti-tumor Action for Cisplatin.
复制标题
铁死亡：顺铂的一种新型抗肿瘤作用
DOI：
10.4143/crt.2016.572
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发表时间：
2018-04
影响因子：
4.6
通讯作者：
Wu G
中科院分区：
文献类型：
--
作者：
Guo J;Xu B;Han Q;Zhou H;Xia Y;Gong C;Dai X;Li Z;Wu G
目的铁凋亡（Ferroptosis）是一种新的细胞死亡调控模式，在形态学、生化学和遗传学上与其他细胞死亡模式完全不同。本研究评价了经典化疗药物对铁凋亡的治疗作用，包括潜在的机制。材料与方法采用甲基噻唑四氮唑染料摄取法检测细胞活力。利用RNA干扰技术敲除铁响应元件结合蛋白2，聚合酶链反应、western blot检测敲除效率。用相关试剂盒测定细胞内还原型谷胱甘肽水平和谷胱甘肽过氧化物酶活性。流式细胞仪测定细胞内活性氧水平。电镜观察细胞超微结构变化。结果顺铂对A549和HCT 116细胞的凋亡和铁凋亡均有诱导作用。顺铂引起的还原型谷胱甘肽的耗竭和谷胱甘肽过氧化物酶的失活在其潜在机制中起着重要作用。此外，顺铂和erastin的联合治疗显示出显着的协同作用，其抗肿瘤活性。结论铁蛋白在抗肿瘤治疗中有很大的潜力，可以弥补一些经典药物的不足，为临床应用开辟新的途径。
Purpose Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. This study evaluated the therapeutic role of ferroptosis in classic chemotherapy drugs, including the underlying mechanism. Materials and Methods Cell viabilitywas detected by using the methylthiazoltetrazlium dye uptake method. RNAiwas used to knockout iron-responsive element binding protein 2, and polymerase chain reaction, western blot was used to evaluate the efficiency. Intracellular reduced glutathione level and glutathione peroxidases activitywere determined by related assay kit. Intracellularreactive oxygen species levelswere determined by flowcytometry. Electron microscopywas used to observe ultrastructure changes in cell. Results Among five chemotherapeutic drugs screened in this study, cisplatin was found to be an inducer for both ferroptosis and apoptosis in A549 and HCT116 cells. The depletion of reduced glutathione caused by cisplatin and the inactivation of glutathione peroxidase played the vital role in the underlying mechanism. Besides, combination therapy of cisplatin and erastin showed significant synergistic effect on their anti-tumor activity. Conclusion Ferroptosis had great potential to become a new approach in anti-tumor therapies and make up for some classic drugs, which open up a new way for their utility in clinic.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
5.8
作者：
Ferry, KV;Hamilton, TC;Johnson, SW
通讯作者：
Johnson, SW
影响因子：
9.7
作者：
Roh, Jong-Lyel;Kim, Eun Hye;Shin, Daiha
通讯作者：
Shin, Daiha
影响因子：
11.5
作者：
Massarelli, Erminia;Varella-Garcia, Marileila;Wistuba, Ignacio I.
通讯作者：
Wistuba, Ignacio I.
影响因子：
13.8
作者：
ZAMBLE, DB;LIPPARD, SJ
通讯作者：
LIPPARD, SJ