当前位置: X-MOL 学术Biochem. Biophys. Res. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
SIRT6 silencing overcomes resistance to sorafenib by promoting ferroptosis in gastric cancer
Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2021-08-30 , DOI: 10.1016/j.bbrc.2021.08.080
Shunv Cai 1 , Shuang Fu 1 , Weikang Zhang 1 , Xiaohong Yuan 1 , Yun Cheng 1 , Jun Fang 1
Affiliation  

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.



中文翻译:

SIRT6沉默通过促进胃癌铁死亡克服索拉非尼耐药

索拉非尼是一种酪氨酸激酶抑制剂,对包括胃癌 (GC) 在内的各种癌症具有抗肿瘤作用。然而,索拉非尼的临床应用往往受到耐药性的阻碍。Sirtuins 6 (SIRT6) 是 NAD (+) 依赖性酶的 Sirtuin 家族的成员,这些酶与各种生物活动密切相关。这项研究表明,SIRT6 沉默通过促进铁死亡(一种新的细胞死亡形式)克服了索拉非尼耐药性。从机制上讲,SIRT6 抑制导致 Keap1/Nrf2 信号通路失活和 GPX4 下调。GPX4 的过表达或 Keap1/Nrf2 的激活逆转了 SIRT6 下调对索拉非尼诱导的铁死亡的影响。因此,

更新日期:2021-08-30
down
wechat
bug