Toxicogenomics Team, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
J Biochem Mol Toxicol. 2010 Jul-Aug;24(4):260-9. doi: 10.1002/jbt.20334.
In this study, we determined whether p53 expression affected the sensitivity of non-small cell lung cancer (NSCLC) and colon cancer cells to bleomycin (BLM). Two human NSCLC cell lines (A549 expressing wild-type p53 and p53-null H1299) and two colon cancer cell lines (HCT116 p53+/+ and its p53 deficient subline HCT116 p53-/-) were subjected to treatment with BLM. Cells were treated with various concentrations of BLM, and cellular viability was assessed by formazan assay. To investigate the role of p53 in BLM sensitivity, we transduced cells with adenovirus with wild-type p53, dominant-negative p53, and GFP control, and analyzed the effect on cellular viability. Cells expressing wild-type p53 were more sensitive to BLM than p53-null cells in both NSCLC and colon cancer cells. Sensitivity to BLM of the cells with wild-type p53 was reduced by overexpression of dominant-negative p53, while BLM sensitivity of p53-null cells was increased by wild-type p53 in both NSCLC cells and colon cancer cells. In conclusion, our data show that p53 sensitizes all four cancer cells lines tested to BLM toxicity and overexpression of p53 confers sensitivity to the cytotoxic activity of the anticancer agent in p53-null cells.
在这项研究中，我们确定了 p53 表达是否影响非小细胞肺癌 (NSCLC) 和结肠癌细胞对博来霉素 (BLM) 的敏感性。我们用 BLM 处理了两种人 NSCLC 细胞系（表达野生型 p53 的 A549 和 p53 缺失的 H1299）和两种结肠癌细胞系（p53+/+的 HCT116 和其 p53 缺失亚系 HCT116 p53-/-）。用博来霉素处理细胞，用甲臜法评估细胞活力。为了研究 p53 在 BLM 敏感性中的作用，我们用携带野生型 p53、显性失活型 p53 和 GFP 对照的腺病毒转导细胞，并分析对细胞活力的影响。在 NSCLC 和结肠癌细胞中，表达野生型 p53 的细胞比 p53 缺失细胞对 BLM 更敏感。在 NSCLC 细胞和结肠癌细胞中，过表达显性失活型 p53 降低了 p53 野生型细胞对 BLM 的敏感性，而野生型 p53 增加了 p53 缺失细胞对 BLM 的敏感性。总之，我们的数据表明，p53 使所有四种被测试的癌细胞系对 BLM 毒性敏感，而过表达 p53 使 p53 缺失细胞对抗癌剂的细胞毒性活性敏感。
