通过调节ASK-1/JNK1通路,TRAIL使非小细胞肺癌易患铁亡
Xiaofang Liu1, Huiqian Deng1, Mi Huang1
1Department III of Geriatrics, The Third Hospital of Changsha, No. 176, Labor West Road, Changsha, 410000, Hunan Province, China.
Discover oncology
|February 21, 2024
概括
过度表达与TNF相关的诱导亡的配体 (TRAIL) 在非小细胞肺癌 (NSCLC) 细胞中触发铁亡,抑制瘤生长. 这通过ASK-1/JNK1通路发生,提供潜在的新NSCLC疗法.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 非小细胞肺癌 (NSCLC) 仍然是癌症死亡的主要原因.
- 与TNF相关的诱导亡联体 (TRAIL) 的作用及其与NSCLC中铁亡的相互作用尚未完全理解.
- 确定新的治疗点和机制对于改善NSCLC治疗结果至关重要.
研究的目的:
- 研究NSCLC发育中的TRAIL表达和铁化之间的关系.
- 阐明 TRAIL 影响 NSCLC 细胞中铁亡的分子机制.
- 在NSCLC模型中评估TRAIL的治疗潜力.
主要方法:
- 使用西部斑块,RT-qPCR和免疫组织化学来量化TRAIL表达.
- 用CCK-8,伤口愈合和Transwell测试来评估细胞活力,迁移和入侵.
- 测量了 Ferroptosis 标志物,包括不稳定的铁池 (LIP),铁含量,铁质铁 (Fe2+),脂质过氧化和抗氧化酶 (SOD,CAT,MDA). 在体内研究中使用了小鼠瘤异种移植模型.
主要成果:
- 与正常细胞 (BEAS-2B) 相比,NSCLC细胞系 (H1299,NCL-H1395,A549) 中的TRAIL表达显著减少.
- 抑制 TRAIL 表达降低了 NSCLC 细胞活力,迁移和入侵,同时通过增加 LIP,铁,Fe2+和脂质过氧化,减少铁抑制剂 (FTH1,GPX4,SLC7A11) 来促进铁亡.
- TRAIL激活了ASK-1/JNK1通路,并且抑制ASK-1减弱了Trail的抗瘤和诱导铁亡的作用. 在体内,TRAIL抑制了瘤生长和ferroptosis.
结论:
- 过度表达TRAIL会诱导NSCLC细胞中的铁亡,从而产生显著的抗瘤作用.
- 该机制涉及ASK-1/JNK1通路的激活,介导TRAIL诱导的铁亡.
- 这些发现表明,TRAIL是NSCLC治疗的有前途的治疗策略.
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