多酶抑制剂调节结直肠癌细胞中的非构成性蛋白酶表达
Alexander Burov1, Ekaterina Grigorieva1,2, Timofey Lebedev3
1Laboratory of Regulation of Intracellular Proteolysis, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
Frontiers in molecular biosciences
|May 22, 2024
概括
多酶抑制剂增加结直肠癌细胞中的非构成性蛋白酶活性,可能影响免疫反应. 这表明,在基于MKI的癌症治疗过程中,需要仔细考虑.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 免疫学 免疫学 免疫学
背景情况:
- 非构成性蛋白质体在免疫反应和癌症预后中起作用.
- 多酶抑制剂 (MKIs) 在癌症治疗中使用,但它们对结直肠癌中非构成性蛋白酶的作用尚不清楚.
研究的目的:
- 研究MKI (regorafenib, sorafenib) 对结直肠癌中非构成性蛋白酶体表达和活性的影响.
- 通过蛋白酶组调节探索MKI的潜在免疫调节影响.
主要方法:
- 对结直肠癌数据集的生物信息分析.
- 用雷戈拉芬尼和索拉芬尼治疗结直肠癌细胞系.
- 评估蛋白质酶子单元的表达,活性,定位和活性氧物种水平.
主要成果:
- 非构成性蛋白酶表达在BRAF突变结直肠瘤中升高.
- MKI增加了非构成性蛋白酶体活性和合成,诱导氧化应激.
- 索拉费尼布,但不是雷戈拉费尼布,引起了活性非构成性蛋白酶的细胞质聚合.
结论:
- MKI可以调节结直肠癌细胞中的细胞内蛋白酶池.
- 这种调节可能会影响癌症和免疫细胞之间的相互作用.
- 这些发现值得在基于MKI的癌症治疗策略中考虑.
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