Effect of downregulation of survivin expression on radiosensitivity of human epidermoid carcinoma cells
Effect of downregulation of survivin expression on radiosensitivity of human epidermoid carcinoma cells
复制标题
DOI：
10.1016/j.ijrobp.2006.06.049
复制
发表时间：
2006-11-01
影响因子：
7
通讯作者：
Meyn, Raymond E.
中科院分区：
文献类型：
--
作者：
Sah, Nand K.;Munshi, Anupama;Meyn, Raymond E.
目的：survivin作为细胞凋亡抑制蛋白家族的一员，在多种类型的人类癌症中表达升高。高survivin表达与患者预后差和肿瘤对化疗和放疗的耐药性有关。本研究的目的是比较五种靶向survivin的药物对其下调survivin表达的相对能力的放射增敏作用。方法与材料：分别用腺病毒介导的野生型p53、survivin反义、丝裂原活化蛋白激酶抑制剂PD98059、细胞周期蛋白依赖性激酶抑制剂Purvalanol A、组蛋白去乙酰化酶抑制剂trichostatin A处理人表皮样癌细胞A431，通过克隆生存曲线分析测定这些处理的放射线增敏效果，并通过Western blot分析它们抑制survivin表达的能力。结果：所有策略均对A431细胞有放射增敏作用。这种效应与它们下调生存素的能力有关。结论：survivin的表达似乎赋予了一种放射耐药表型，这种表型可以通过几种临床可实现的策略来克服，这些策略可以特异性或非特异性地靶向survivin。(c) 2006爱思唯尔公司
Purpose: The expression of survivin, a member of the inhibitor-of-apoptosis protein family, is elevated in many types of human cancer. High survivin expression has been associated with poor patient prognosis and tumor resistance to chemotherapy and radiotherapy. The purpose of this study was to compare the radiosensitizing effects of five agents that target survivin on their relative ability to downregulate survivin expression.Methods and Materials: The human epidermoid carcinoma cell line A431 was treated with adenoviral-mediated wild-type p53, antisense to survivin, the mitogen-activated protein kinase inhibitor PD98059, the cyclin-dependent kinase inhibitor Purvalanol A, or the histone deacetylase inhibitor trichostatin A. The radiosensitizing effects of these treatments were determined by clonogenic survival curve analysis and their abilities to suppress survivin expression by Western blot analysis.Results: All the strategies were shown to radiosensitize A431 cells. This effect correlated with their abilities to downregulate survivin.Conclusion: Expression of survivin appears to confer a radioresistant phenotype that can be overcome using several clinically achievable strategies that target survivin either specifically or nonspecifically. (c) 2006 Elsevier Inc.