铅诱导人肝癌（HepG）细胞的细胞周期阻滞：氧化应激、p53及A的参与
Lead-Induced Cell Cycle Arrest in Human Liver Carcinoma (HepG) Cells: Involvement of oxidative stress, p53 and A.
作者信息
Yedjou Clement G, Tchounwou Paul B
机构信息
Cellomics and Toxicogenomics Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi, USA.
出版信息
Met Ions Biol Med. 2011;11:242-246.
BACKGROUND
Recent studies in our laboratory have demonstrated that lead is cytotoxic to human liver carcinoma (HepG) cells, showing a 48 h-LD of 35.5 ± 9.2ug/mL. However, its molecular mechanisms of toxicity are still largely unknown. Hence, the aim of the present study was to use HepG cells as a test model to investigate the molecular mechanisms of lead-induced oxidative stress and modulation of cellular response proteins.
METHODS
To achieve this goal, we performed lipid peroxidation assay for malondialdehyde (MDA) determination, western blot and densitometric analyses for genes and related proteins expression in human liver carcinoma cells.
RESULTS
Data obtained from the lipid peroxidation assay demonstrated a significant increase (p ≤ 0.05) of MDA levels in lead-treated HepG cells compared to control cells. Western Blot analysis showed a strong dose-response relationship with regard to p53 expression, and a significant repression in in lead-treated cells.
CONCLUSIONS
Findings from this research indicate that lead is able to cause oxidative stress, cell cycle arrest through activation of the 53-kDa tumor suppressor protein and down regulation of the A protein in human liver carcinoma (HepG) cells.
背景
我们实验室最近的研究表明，铅对人肝癌（HepG）细胞具有细胞毒性，48小时半数致死剂量为35.5±9.2微克/毫升。然而，其毒性的分子机制仍 largely未知。因此，本研究的目的是以HepG细胞为测试模型，研究铅诱导氧化应激和调节细胞反应蛋白的分子机制。
方法
为实现这一目标，我们进行了脂质过氧化测定以检测丙二醛（MDA），并进行了蛋白质印迹和光密度分析以检测人肝癌细胞中基因和相关蛋白的表达。
结果
脂质过氧化测定获得的数据表明，与对照细胞相比，铅处理的HepG细胞中MDA水平显著升高（p≤0.05）。蛋白质印迹分析显示p53表达呈强剂量反应关系，且铅处理细胞中显著抑制。
结论
本研究结果表明，铅能够在人肝癌（HepG）细胞中通过激活53-kDa肿瘤抑制蛋白和下调A蛋白引起氧化应激、细胞周期停滞。
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