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细菌DnaK降低了抗癌药物西斯和5FU的活性
Francesca Benedetti1,2, Emmanuel F Mongodin3, Jonathan H Badger4
1Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
Journal of translational medicine
|March 13, 2024
概括
癌症相关细菌 (CAB) 可以降低化疗的有效性. 用ARV-1502准细菌DnaK,一种破坏瘤抑制剂的蛋白质,可以恢复抗癌药物的疗效,提供基于微生物组的个性化疗法.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 生物化学 生物化学
背景情况:
- 化疗疗效率通常受到癌症相关细菌 (CAB) 的限制,这些细菌会损害瘤抑制功能.
- 以前已经证明,细菌伴侣蛋白DnaK的菌质发酵素会损害对抗癌药物反应至关重要的p53活动.
研究的目的:
- 研究细菌DnaK蛋白在调节p53依赖化学疗法的有效性方面的作用.
- 评估DnaK结合 (ARV-1502) 在恢复抗癌药物疗效方面的治疗潜力.
- 用TCGA数据集探索细菌DnaK在人类癌症中的临床相关性.
主要方法:
- 来自DnaK敲入小鼠模型的癌症细胞系和原发性瘤细胞被细菌DnaK治疗,然后用西斯或5FU治疗.
- 细胞存活率根据DnaK结合ARV-1502.2的存在或不存在进行评估.
- 来自TCGA的人类癌症测序数据被分析,以确定携带DnaK蛋白质的CAB,与M. fermentans DnaK具有很高的相似性.
主要成果:
- 发现Mycoplasma发酵素和Fusobacterium核素DnaK蛋白质都降低了西斯和5FU的抗癌疗效.
- 服用ARV-1502有效地恢复了这些化疗剂的抗癌活性.
- 鉴定出Fusobacterium nucleatum是一种表达DnaK蛋白的CAB,与M. fermentans DnaK具有显著的氨基酸相似性.
结论:
- 来自CAB的细菌DnaK蛋白可以显著降低标准化疗的有效性.
- 用ARV-1502等酸准细菌DnaK是个性化癌症治疗的一个有希望的策略.
- 这些发现支持开发基于微生物组的方法,以克服癌症患者的化疗耐药性.
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