增加脂质生成对于六价转化肺细胞和异种移植瘤生长非常重要
James T F Wise1,2,3,4, Kazuya Kondo5
1Wise Laboratory of Nutritional Toxicology and Metabolism, School of Nutrition and Food Sciences, College of Agriculture, Louisiana State University, 269 Knapp Hall, Baton Rouge, LA 70803, USA.
International journal of molecular sciences
|December 9, 2023
概括
六价 (Cr(VI)) 暴露会增加脂肪生成,这对癌细胞生长至关重要. 抑制脂肪酸合成酶 (FASN) 降低了Cr(VI) 转化细胞的增殖和瘤的发展,突出了FASN作为治疗点.
科学领域:
- 环境健康科学 环境健康科学
- 分子致癌症的产生.
- 生物化学 生物化学
背景情况:
- 六价 (Cr(VI)) 是已知的人类致癌物,与反应性氧物种和DNA损伤有确定的联系.
- 增加脂质生成的作用,癌症的标志,在Cr (VI) 诱导的致癌症仍然未得到充分研究.
- 了解Cr (VI) 致癌机制对于制定有针对性的预防和治疗策略至关重要.
研究的目的:
- 调查增加脂质发生在Cr (VI) 诱导的肺癌发生中的作用.
- 为了确定关键脂原蛋白在Cr (VI) 转化细胞和人类肺部瘤中的表达.
- 评估向脂肪酸合成酶 (FASN) 在CrVI诱导的癌症中的治疗潜力.
主要方法:
- 人类肺细胞系 (BEAS-2B,BEP2D,WTHBF-6) 的Cr(VI诱导的转化.
- 测量脂质生成,脂肪酸氧化和脂质滴滴的形成.
- 通过西部斑块和在人类肺瘤组织中分析脂质蛋白表达 (ACLY,ACC1,FASN).
- 药理抑制 (C75) 和基因淘汰 (shRNA) 的FASN在CrVI转化细胞.
- 评估细胞生长,软菌殖民地形成和异种移植瘤的发展.
主要成果:
- 经过Cr(VI) 转化的肺细胞显著增加了脂质生成和ACLY,ACC1和FASN的高表达.
- 在染色体工人的肺瘤中也观察到增加了ACLY,ACC1和FASN表达.
- 抑制或淘汰FASN显著降低了Cr(VI) 转化细胞的增殖,软的生长和异种移植瘤的形成.
结论:
- 在体外,Cr(VI) 转化导致脂质生成的增加,这对于转化细胞的生长和恶性特性至关重要.
- 脂肪酸合成酶 (FASN) 是Cr(VI) 诱导的细胞转化和瘤发生的关键媒介.
- 向FASN代表了一种有前途的治疗策略,用于预防或治疗CrVI诱导的肺癌.
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