P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines
P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines
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DOI：
10.1002/hed.10274
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发表时间：
2003-08-01
影响因子：
2.9
通讯作者：
Carey, TE
中科院分区：
文献类型：
--
作者：
Bradford, CR;Zhu, SB;Carey, TE
背景。头颈癌器官保存治疗成功的一个关键因素可能是选择对化疗和放疗有反应的肿瘤。以往在患者中的研究结果表明，过表达p53的肿瘤比不过表达p53的肿瘤对化疗更敏感。为了确定p53突变与体外顺铂敏感性的关系，我们分析了23株头颈部鳞状细胞癌（HNSCC）细胞株的顺铂敏感性、p53表达和p53突变状态。在测试的23个细胞系中，有13个发现了p53基因的突变。p53基因的突变与p53蛋白的高水平表达显著相关。突变型p53细胞系的平均ID50（抑制50%细胞生长所需的药物剂量）为6.8 muM，而野生型p53细胞系的平均ID50为13.7 muM。这些体外数据支持p53肿瘤抑制基因突变作为HNSCC对顺铂反应的标志物的作用。(C) 2003 Wiley期刊有限公司
Background. A critical factor for successful organ preservation treatment in head and neck cancer may be selecting tumors that respond to chemotherapy and radiation. Previous results in patients indicated that tumors that overexpressed p53 were more sensitive to chemotherapy than those that did not overexpress p53.Methods. To determine the relationship of p53 mutations to sensitivity to cisplatin in vitro, 23 head and neck squamous cell carcinoma (HNSCC) cell lines were analyzed for cisplatin sensitivity, p53 expression, and p53 mutation status.Results. Mutations of the p53 gene were identified in 13 of 23 of the cell lines tested. Mutation of the p53 gene was significantly associated with high levels of expression of the p53 protein. The average ID50 (drug dose required to inhibit 50% of cell growth) for cell lines with mutant p53 was 6.8 muM, whereas the average ID50 for cell lines with wild-type p53 was 13.7 muM.Conclusions. These in vitro data support a role for mutation of the p53 tumor suppressor gene as a marker for response to cisplatin in HNSCC. (C) 2003 Wiley Periodicals, Inc.