在p53依赖的HIF-1α/自中介糖解中,支持Cr(VI) 诱导的细胞生长和细胞迁移
Yanqiu Yang1, Bin Song2, Minna Guo1
1Department of Occupational and Environmental Health, Dalian Medical University, No. 9 W. Lvshun South Road, Dalian 116044, China.
六价 (Cr(VI)) 暴露会增加肺癌细胞中缺氧诱导因子-1α (HIF-1α),通过糖解和自驱动瘤生长. 这种途径依赖p53,与正常细胞不同.
科学领域:
- 毒理学 毒理学 毒理学
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 六价 (Cr(VI)) 是一个已知的致癌物质.
- 缺氧诱导因子-1α (HIF-1α) 在瘤发育中至关重要.
研究的目的:
- 为了研究HIF-1α在Cr(VI) 诱导的细胞变化的作用.
- 阐明肺细胞中Cr(VI) 致癌的机制.
主要方法:
- 细胞培养 (A549,HELF细胞) 和动物模型 (BALB/c小鼠).
- 使用Cr(VI),HIF-1α抑制剂 (YC-1),HIF-1α诱导剂 (CoCl2) 和p53诱导剂 (RITA) 的治疗.
- 对自,糖解,细胞生长和蛋白质表达的分析 (HIF-1α,p53,LC3-II).
主要成果:
- 在A549细胞和小鼠肺部中增加了HIF-1α表达,但不是HELF细胞.
- 在A549细胞中,HIF-1α介导的Cr(VI) 诱导的自,糖解和细胞生长.
- p53影响了Cr(VI) 对HIF-1α的影响,在A549细胞中较低的p53.
结论:
- 一个p53-依赖的HIF-1α/自途径驱动了Cr(VI) 暴露的A549细胞中的糖解和细胞生长.
- 这种机制有助于Cr (VI) 诱导的肺癌发生.
- 自,但不是HIF-1α,在正常的HELF细胞中诱导糖解.
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