USP22-JMJD8轴促进了Lenvatinib在肝细胞癌中的耐药性
1Qingdao Medical College, Qingdao University, Qingdao 266071, China.
Biochimica et biophysica acta. Molecular cell research
|October 28, 2023
概括
在肝细胞癌 (HCC) 中对伦瓦提尼布的耐药性是一个重大挑战. 这项研究确定USP22和JMJD8是伦瓦提尼布耐药性的关键参与者,提供潜在的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 伦瓦提尼布是先进肝细胞癌 (HCC) 的一线治疗方法.
- 药物耐药性限制了伦瓦替尼在HCC治疗中的长期疗效.
- 在HCC中Lenvatinib耐药性背后的机制需要进一步阐明.
研究的目的:
- 研究伦瓦替尼布在HCC中耐药性的分子机制.
- 确定克服伦瓦替尼布耐药性的新型治疗点.
主要方法:
- 构建了耐伦瓦替尼布的HCC细胞系.
- 分析了蛋白质表达水平 (USP22,JMJD8,茎状标志物).
- 进行了基因淘汰和过度表达实验.
- 在体内进行的动物研究 (裸体小鼠).
主要成果:
- USP22和JMJD8在Lenvatinib耐药的HCC细胞中被上调.
- 耐药细胞表现出增加的干细胞标志物 (CD133,C-MYC,BMI1,β-CATENIN).
- 通过USP22 Knockdown,减少了细胞入侵,迁移和干细胞,并促进了耐药细胞的亡.
- USP22和JMJD8形成了一个功能轴,调节伦瓦提尼布耐药性.
结论:
- USP22-JMJD8轴对Lenvatinib在HCC中的耐药性至关重要.
- 针对USP22-JMJD8轴可能会提高伦瓦替尼的疗效.
- USP22-JMJD8代表了HCC治疗的潜在药物设计目标.
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