依维莫司
舒尼替尼
肾细胞癌
索拉非尼
癌症研究
PI3K/AKT/mTOR通路
生物
药理学
医学
肿瘤科
信号转导
细胞生物学
肝细胞癌
作者
Yangyun Wang,Guowei Shi,Shi Shufen,Jie Yao,Ran Yu,Yu Ren
出处
期刊:Gene
[Elsevier]
日期:2022-01-01
卷期号:809: 145992-145992
被引量:17
标识
DOI:10.1016/j.gene.2021.145992
摘要
Renal cell carcinoma (RCC) is a common type of urological cancer and is often diagnosed at an advanced stage. Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), is used as second-line therapy for sorafenib- or sunitinib-refractory metastatic RCC. However, the clinical benefits of Everolimus are often hampered by drug resistance. Ferroptosis is a novel form of regulated cell death that has recently been implicated in the development and therapeutic responses to different cancers. RSL3 ((1S,3R)-RSL3) and Erastin are two experimental compounds that can induce ferroptosis. In the present study, we evaluated the anti-tumor effects of Everolimus in combination with RSL3 or Erastin in RCC. Everolimus and RSL3/Erastin could synergistically inhibit the viability and induce ferroptosis in RCC cells. Mechanistically, the inhibition of the mTOR-4EBP1 axis was found to be essential for the synergistic effects of Everolimus and RSL3/Erastin. Moreover, the forced expression of GPX4 abrogated ferroptosis induced by the combined treatment of Everolimus and RSL3/Erastin. Taken together, these results demonstrated that Everolimus in combination with RSL3/Erastin is a promising therapeutic option for RCC treatment and it may also help to overcome the limitation in clinical applicability of Everolimus.
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