香烟烟雾提取物通过人类支气管上皮细胞的c-MET酸化诱导恶性转化和DNA损伤
Li Wang1, Jin Chen2, Qianhui Li1
1School of Public Health, North Sichuan Medical College, Nanchong 637000, China; School of Pharmacy, North Sichuan Medical College, Nanchong 637000, China.
Ecotoxicology and environmental safety
|September 1, 2024
概括
香烟烟雾提取物 (CSE) 激活c-MET信号,导致DNA损伤和肺细胞中不受控制的细胞生长. 抑制c-MET可以预防吸烟引起的肺部疾病.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 毒理学 毒理学 毒理学
背景情况:
- 香烟烟雾含有致癌物质,会导致DNA受损.
- 过度激活c-MET (受体氨酸激酶) 与癌症和DNA损伤有关,但机制尚不清楚.
研究的目的:
- 研究香烟烟雾提取物 (CSE) 诱导的人类支气管上皮细胞 (BEAS-2B) 恶性转化和DNA损伤的机制.
主要方法:
- 用CSE处理的BEAS-2B细胞.
- 分析了基因表达 (mRNA) 和蛋白质水平 (γ-H2AX,c-MET,ATM,ATR,CHK1,CHK2) 的情况.
- 使用了c-MET抑制剂 (PHA665752),c-MET抑制和c-MET过度表达.
主要成果:
- CSE上调调节了c-MET通路基因,增加了DNA损伤标志物γ-H2AX,并促进了不受控制的增殖.
- 在CSE激活的DNA损伤反应激酶 (ATM,ATR,CHK1,CHK2) 和c-MET酸化.
- 抑制或击倒c-MET可以减少CSE诱导的DNA损伤;c-MET过度表达会使其恶化.
结论:
- c-MET酸化与CSE诱导的DNA损伤有关.
- 准c-MET可能为预防和治疗吸烟相关的肺部疾病提供了一种策略.
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