氨酸的限制降低了肺癌的进展,并增加了化疗反应
Kassandra J Naughton1, Xiulong Song1, Avery R Childress1
1Department of Toxicology and Cancer Biology, University of Kentucky, Lexington KY 40536.
bioRxiv : the preprint server for biology
|July 9, 2024
概括
氨酸的限制减缓了小鼠的侵袭性非小细胞肺癌 (NSCLC) 的进展. 这种饮食干预增强了卡博普拉丁的疗效,并防止了血统切换,为NSCLC患者提供了一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 癌症中的代谢途径
- 饮食干预和癌症治疗方法
背景情况:
- 侵袭性癌症,包括非小细胞肺癌 (NSCLC),死亡率高.
- 通过饮食干预来准瘤代谢是一种有前途的策略,可以改善癌症治疗结果.
- KRAS/Lkb1突变NSCLC是一种具有有限治疗选择的侵袭性亚型.
研究的目的:
- 调查 metionin 限制 (MR) 对 KRAS/Lkb1 突变性 NSCLC 进展和碳白治疗疗效的影响.
- 阐明潜在的机制,包括对瘤血统,免疫微环境和氨酸β-合成酶 (CBS) 表达的影响.
- 评估MR作为NSCLC的辅助疗法的潜力.
主要方法:
- 使用了一种本土KRAS/Lkb1突变NSCLC小鼠模型.
- 作为一种饮食干预措施,给予 metionin 限制 (MR).
- 评估了瘤进展,卡博普拉丁治疗疗效,瘤免疫微环境 (TIME),细胞循环停止,细胞亡和T细胞增殖.
- 在人类NSCLC细胞系和患者瘤中分析了cystathionine-β-synthase (CBS) 表达.
主要成果:
- 在NSCLC小鼠模型中,氨酸限制显著降低了瘤进展,并增加了碳酸的疗效.
- 核磁共振阻止了血统切换,并减少了瘤透中性粒细胞,改变了时间.
- LKB1突变与改变的CBS表达和碳烯抗性有关,这种抗性可以被MR部分挽救.
- CBS表达与吸烟和特定的NSCLC亚型相关,这表明它在氧化应激和血统命运中发挥了作用.
结论:
- 氨酸限制是一种可行的饮食干预措施,可以减缓侵袭性NSCLC中的瘤生长.
- MR增强了卡博普拉丁化疗的疗效,并调节了瘤免疫微环境.
- 准 metionin代谢和CBS表达,为NSCLC提供了一个新的治疗途径.
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