福基转移酶4通过NF-κB信号通路对化学抵抗的P-gp表达进行上调
Zixuan Cai1, Tomoya Isaji2, Caixia Liang3
1Division of Regulatory Glycobiology, Graduate School of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan.
Biochimica et biophysica acta. General subjects
|December 26, 2024
概括
通过NF-κB通路增强P-糖蛋白,FUT4的上调会增加化学抵抗. 向FUT4可能会在癌症治疗中克服多药性耐药性.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 多种药物耐药性 (MDR) 是化疗中的一个主要挑战.
- N-乙葡萄糖氨基基转移酶III (GnT-III) 负面调节化学抵抗.
- 在抗胺素 (ADR) 细胞中观察到糖化增加.
研究的目的:
- 调查福克西化,特别是FUT4在阿德里亚米辛耐药性 (ADR) 中的作用.
- 阐明FUT4影响化学抵抗的机制.
- 评估FUT4作为MDR的潜在治疗点.
主要方法:
- 莱克斑,西部斑,以及流动细胞测量用于化分析.
- 对基因表达进行定量PCR (qPCR).
- 通过CRISPR/Cas9生成FUT4淘汰 (KO) 的ADR细胞.
- 细胞毒性和药物流量测定.
主要成果:
- 在ADR细胞中,FUT4和LeX抗原的表达被上调.
- FUT4 KO降低了P-葡萄糖蛋白 (P-gp) 水平,并增加了药物敏感性.
- 恢复FUT4逆转了P-gp表达,药物排放和化学抵抗.
- FUT4调节的NF-κB通路信号,特别是p65酸化.
结论:
- 通过NF-κB信号通路,FUT4通过上调P-gp表达来促进化学抵抗.
- FUT4是ADR细胞中化学抵抗的关键调节者.
- FUT4代表了克服MDR的有希望的治疗标.
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