基斯乳化促进肝细胞癌的多药性耐药性,通过与PTEN形成一个积极的反循环
Yuan Zeng1, Haoran Jiang2,3, Zhoufeng Chen1
1Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Cell death & disease
|January 31, 2025
概括
抵抗FOLFOX化疗的肝细胞癌细胞表现出增加的葡萄糖分解. 通过抑制这种代谢途径和向激素乳化-NEDD4-PTEN轴,可以克服药物耐药性.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 分子生物学分子生物学
背景情况:
- 肝细胞癌 (HCC) 用FOLFOX (5-甲,氧沙,叶酸) 治疗受到药物耐药性的挑战.
- 在HCC中驱动oxaliplatin (OXA) 和5-fluorouracil (5-Fu) 耐药性的机制在很大程度上仍未定义.
研究的目的:
- 调查在HCC中OXA和5-Fu耐药性背后的机制.
- 确定潜在的治疗点,以克服HCC的化疗耐药性.
主要方法:
- 建立抗OXA和5-Fu的HCC细胞系.
- 对细胞代谢活动的分析,重点是糖解.
- 通过分子生物学技术,研究基因素乳化,NEDD4和PTEN相互作用.
主要成果:
- 耐药的HCC细胞表现出增强的糖解活性,这推动了恶性进展.
- 抑制糖解抑制了耐药细胞的恶性表型.
- 基因激素乳化,特别是H3K14la,调节基因表达和NEDD4活动.
- 通过乳化调节的NEDD4诱导了PTEN无化和降解,创建了一个反循环,促进了耐药性.
结论:
- 增强的葡萄糖分解和基因素乳糖化-NEDD4-PTEN轴代表了HCC中OXA和5-Fu抵抗的共享机制.
- 向糖解或乳糖化途径提供了一种潜在的策略,以克服HCC患者的化疗耐药性.
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