Targeting apoptosis to overcome cisplatin resistance: A translational study in head and neck cancer
Targeting apoptosis to overcome cisplatin resistance: A translational study in head and neck cancer
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DOI：
10.1016/j.ijrobp.2007.05.080
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发表时间：
2007-01-01
影响因子：
7
通讯作者：
Bradford, Carol R.
中科院分区：
文献类型：
--
作者：
Bauer, Joshua A.;Kumar, Bhavna;Bradford, Carol R.
目的：顺铂耐药仍然是晚期头颈部鳞状细胞癌（HNSCC）患者器官保留和生存的障碍。治疗顺铂耐药HNSCC的靶向疗法正在开发中。方法与材料：对顺铂敏感亲代HNSCC细胞系及顺铂耐药后代进行研究。预处理HNSCC活检构建组织微阵列，对p53和Bcl-xL进行染色。结果：顺铂耐药的HNSCC细胞系具有野生型p53和高水平的Bel-xL。野生型p53在低Bcl-xL细胞系中的表达增强顺铂敏感性。Bcl-xL和野生型p53的表达均导致肿瘤细胞产生顺铂耐药。肿瘤表达低水平p53和Bcl-xL的患者享有最好的器官保存和无病生存，而肿瘤表达低水平p53和高水平Bcl-xL的患者预后最差。抑制Bcl-xL或激活p53功能的新型药物可能针对顺铂耐药的HNSCC。结论：HNSCC的顺铂耐药至少部分是由高Bcl-xL和功能性p53介导的。(C) 2007爱思唯尔公司
Purpose: Cisplatin resistance remains a barrier to organ-sparing and survival of patients with advanced head and neck squamous cell carcinoma (HNSCC). Targeted therapies to overcome cisplatin-resistant HNSCC are being developed.Methods and Materials: Cisplatin-sensitive parental HNSCC cell lines and cisplatin-resistant progeny were studied. Pretreatment HNSCC biopsies were used to construct tissue microarrays which were stained for p53 and Bcl-xL.Results: HNSCC cell lines selected for cisplatin resistance had wild-type p53 and high levels of Bel-xL. Expression of wild-type p53 in cell lines with low Bcl-xL enhanced cisplatin sensitivity. Expression of both Bcl-xL and wildtype p53 caused tumor cells to become cisplatin resistant. Patients whose tumors expressed low levels of p53 and Bcl-xL enjoyed the best organ preservation and disease-free survival whereas patients whose tumors expressed low levels of p53 and high levels of Bcl-xL had the worst outcome. Novel agents that inhibit Bcl-xL or activate p53 function may target cisplatin-resistant HNSCC.Conclusion: Cisplatin resistance in HNSCC is mediated, at least in part, by high Bcl-xL and functional p53. (C) 2007 Elsevier Inc.