SIRT6 silencing overcomes resistance to sorafenib by promoting ferroptosis in gastric cancer.
Biochem Biophys Res Commun
; 577: 158-164, 2021 11 05.
Article
em En
| MEDLINE
| ID: mdl-34530350
ABSTRACT
Sorafenib is a tyrosine kinase inhibitor that shows anti-tumour effects against various cancers including gastric cancer (GC). However, the clinical application of sorafenib is often hampered by drug resistance. Sirtuins 6 (SIRT6) is a member of the Sirtuin family of NAD (+)-dependent enzymes that are critically involved in various biological activities. This study presents that SIRT6 silencing overcomes sorafenib resistance by promoting ferroptosis, which is a novel form of cell death. Mechanistically, SIRT6 inhibition led to the inactivation of the Keap1/Nrf2 signalling pathway and downregulation of GPX4. The overexpression of GPX4 or activation of Keap1/Nrf2 reverses the effects of the downregulation of SIRT6 on sorafenib-induced ferroptosis. Thus, targeting the SIRT6/Keap1/Nrf2/GPX4 signalling pathway may be a potential strategy for overcoming sorafenib resistance in GC.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Resistencia a Medicamentos Antineoplásicos
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Sirtuínas
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Interferência de RNA
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Sorafenibe
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Ferroptose
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article