通过抗氧化剂稳定BACH1刺激肺癌转移
Clotilde Wiel1, Kristell Le Gal2, Mohamed X Ibrahim3
1Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden; Sahlgrenska Cancer Center, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
Cell
|July 2, 2019
概括
抗氧化剂如N-乙半氨酸和维生素E通过稳定BACH1促进肺癌转移,从而增加葡萄糖代谢. 针对BACH1可以防止这种抗氧化剂驱动的传播.
科学领域:
- 癌症学
- 代谢过程
- 分子生物学
背景情况:
- 癌细胞必须克服氧化压力才能发展成瘤.
- 抗氧化剂可以减轻氧化压力,促进肺部瘤的早期生长.
- 抗氧化剂对肺癌转移的影响尚不清楚.
研究的目的:
- 研究长期抗氧化剂补充剂对KRAS驱动的肺癌转移的影响.
- 阐明抗氧化剂影响肺癌转移的分子机制.
主要方法:
- 在小鼠模型中长期补充N-乙半氨酸和维生素E.
- 分析自由血红蛋白水平,BACH1转录因子稳定性和葡萄糖代谢标记物 (Hexokinase 2,Gapdh).
- 针对BACH1表达并评估其对小鼠和人类肺癌细胞的糖解和转移的影响.
主要成果:
- 抗氧化剂补充促进了KRAS驱动的肺癌转移.
- 抗氧化剂降低了自由血红素并稳定了BACH1,从而增加了Hexokinase 2和Gapdh的表达.
- 这导致葡萄糖吸收,糖分解率和乳酸分泌量增加,导致转移.
- 向BACH1使糖分分解正常化,并防止抗氧化剂诱导的转移.
- 即使没有抗氧化剂,单独增加BACH1的表达也会刺激糖分分解和转移.
结论:
- BACH1刺激了依赖于糖溶解的肺癌转移.
- 在降低氧化应激的条件下激活BACH1.
- 向BACH1代表了抗氧化剂加剧的肺癌转移的潜在治疗策略.
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