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布鲁萨托尔通过抑制Nrf2在差异化甲状腺癌中减弱了KRAS诱导的扩散和入侵
Z Gong1,2, L Xue1, A C Vlantis1
1Department of Otorhinolaryngology, Head and Neck Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Journal of endocrinological investigation
|December 7, 2023
概括
核因子红色素2相关因子2 (Nrf2) 在差异化甲状腺癌 (DTC) 中由KRAS上调,促进脱差. 用布鲁萨托尔抑制Nrf2抑制了KRAS驱动的瘤生长,这表明Nrf2是治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 差异化甲状腺癌 (PDTC) 和形甲状腺癌 (ATC) 源于差异化甲状腺癌 (DTC).
- DTC的脱差导致预后不佳和高死亡率.
- Nrf2在KRAS诱导的DTC脱差中的作用尚不清楚.
研究的目的:
- 研究Nrf2在KRAS介导的DTC脱差中的功能.
- 为了确定Nrf2是否是甲状腺癌中KRAS的下游目标.
- 评估Nrf2作为KRAS驱动的甲状腺癌的潜在治疗标.
主要方法:
- 使用了两个DTC细胞系 (BCPAP和WRO) 具有野生类型KRAS (KRAS-WT) 和KRAS G12V突变 (KRAS-G12V) 的过度表达.
- 评估了细胞的增殖,入侵和形态.
- 通过免疫组织化学 (IHC) 和西式涂抹检查Nrf2表达.
- 服用Nrf2抑制剂Brusatol并进行异种移植试验.
主要成果:
- 克拉斯过度表达增加了DTC细胞的增殖和入侵,诱导了侵略性形态.
- 在KRAS-WT和KRAS-G12V上调DTC细胞中的Nrf2表达.
- 在甲状腺癌组织中,nrf2蛋白水平明显高于正常组织,与预后不佳相关.
- 布鲁萨托尔治疗抑制了KRAS诱导的增殖和侵入,并在体内抑制了瘤的生长.
结论:
- Nrf2是甲状腺癌中KRAS的下游分子.
- Nrf2在KRAS介导的DTC脱差中起着至关重要的作用.
- 抑制Nrf2代表了对KRAS驱动的甲状腺癌的有前途的治疗策略.
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