PMID- 34648917
OWN - NLM
STAT- MEDLINE
DCOM- 20211208
LR  - 20211214
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 809
DP  - 2022 Jan 30
TI  - Everolimus accelerates Erastin and RSL3-induced ferroptosis in renal cell 
      carcinoma.
PG  - 145992
LID - S0378-1119(21)00587-4 [pii]
LID - 10.1016/j.gene.2021.145992 [doi]
AB  - 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.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Yangyun, Wang
AU  - Yangyun W
AD  - Department of Urology, Shanghai Fifth People's Hospital, Fudan University, 
      Shanghai 200240, People's Republic of China.
FAU - Guowei, Shi
AU  - Guowei S
AD  - Department of Urology, Shanghai Fifth People's Hospital, Fudan University, 
      Shanghai 200240, People's Republic of China.
FAU - Shufen, Shi
AU  - Shufen S
AD  - Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 
      Yinzhou No 2. Hospital, Ningbo, China.
FAU - Jie, Yao
AU  - Jie Y
AD  - Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key 
      Laboratory of Pathophysiology, School of Medical, Ningbo University, Ningbo, 
      China.
FAU - Rui, Yu
AU  - Rui Y
AD  - Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key 
      Laboratory of Pathophysiology, School of Medical, Ningbo University, Ningbo, 
      China.
FAU - Yu, Ren
AU  - Yu R
AD  - Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, Ningbo 
      Yinzhou No 2. Hospital, Ningbo, China. Electronic address: nbrenyu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20211011
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (Carbolines)
RN  - 0 (Piperazines)
RN  - 0 (RSL3 compound)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (erastin)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Carbolines/administration & dosage/pharmacology
MH  - Carcinoma, Renal Cell/*drug therapy/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Everolimus/administration & dosage/pharmacology
MH  - Ferroptosis/*drug effects/physiology
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/metabolism/pathology
MH  - Lipid Peroxidation/drug effects
MH  - Phospholipid Hydroperoxide Glutathione Peroxidase/genetics/metabolism
MH  - Piperazines/administration & dosage/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Erastin
OT  - Everolimus
OT  - Ferroptosis
OT  - RSL3
OT  - Renal cell carcinoma
OT  - mTOR
EDAT- 2021/10/15 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/10/14 20:13
PHST- 2021/07/20 00:00 [received]
PHST- 2021/09/20 00:00 [revised]
PHST- 2021/10/04 00:00 [accepted]
PHST- 2021/10/15 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/10/14 20:13 [entrez]
AID - S0378-1119(21)00587-4 [pii]
AID - 10.1016/j.gene.2021.145992 [doi]
PST - ppublish
SO  - Gene. 2022 Jan 30;809:145992. doi: 10.1016/j.gene.2021.145992. Epub 2021 Oct 11.