Adenoviral-E2F-1 radiosensitizes p53wild-type and P53null human prostate cancer cells
Adenoviral-E2F-1 radiosensitizes p53wild-type and P53null human prostate cancer cells
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DOI：
10.1016/j.ijrobp.2005.04.033
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发表时间：
2005-09-01
影响因子：
7
通讯作者：
Pollack, A
中科院分区：
文献类型：
--
作者：
Nguyen, KH;Hachem, P;Pollack, A
目的：E2 F-1是一种转录因子，通过诱导细胞凋亡增强多种细胞系的辐射敏感性。然而，关于这种增强是否通过p53依赖性途径介导，存在相互矛盾的数据。此外，E2 F-1在人前列腺癌对辐射的反应中的作用尚未得到很好的表征。在这项研究中，我们研究了腺病毒-E2 F-1（Ad-E2 F-1）对p53（野生型）（LNCaP）和p53（null）（PC 3）前列腺癌细胞系放射敏感性的影响。方法和材料：LNCaP和PC 3细胞用Ad-E2 F-1，腺病毒-荧光素酶（Ad-Luc）对照载体，或腺病毒-p53（Ad-p53）转导。Western blot检测E2 F-1和p53的表达。进行膜联蛋白V和半胱天冬酶3 + 7测定以估计凋亡水平。克隆形成存活测定用于确定总体细胞死亡。通过方差分析确定统计学显著性，使用Bonferroni方法校正多重comparation.Results：Western blot分析证实了用Ad-E2 F-1和Ad-p53转导的功效。Ad-E2 F-1转导显著增强了两种细胞系的凋亡，降低了克隆形成存活率。虽然E2 F-1介导的放射增敏作用是独立的p53状态，这种效果是更明显的p53野生型LNCaP细胞。当PC 3细胞与RT和Ad-E2 F-1的组合与Ad-p53治疗，至少有一个添加剂减少克隆形成survival.Conclusions：我们的研究结果表明，Ad-E2 F-1显着增强p53野生型和p53 null前列腺癌细胞对放射治疗的反应，虽然放射增敏作用更明显的p53的存在。Ad-E2 F-1可能是前列腺癌放射治疗的一个有用的辅助手段。(c)2005年爱思唯尔公司
Purpose: E2F-1 is a transcription factor that enhances the radiosensitivity of various cell lines by inducing apoptosis. However, there are conflicting data concerning whether this enhancement is mediated via p53 dependent pathways. Additionally, the role of E2F-1 in the response of human prostate cancer to radiation has not been well characterized. In this study, we investigated the effect of Adenoviral-E2F-1 (Ad-E2F-1) on the radiosensitivity of p53(wild-type) (LNCaP) and p53(null) (PC3) prostate cancer cell lines.Methods and Materials: LNCaP and PC3 cells were transduced with Ad-E2F-1, Adenoviral-Luciferase (Ad-Luc) control vector, or Adenoviral-p53 (Ad-p53). Expression of E2F-1 and p53 was examined by Western blot analysis. Annexin V and caspase 3 + 7 assays were performed to estimate the levels of apoptosis. Clonogenic survival assays were used to determine overall cell death. Statistical significance was determined by analysis of variance, using the Bonferroni method to correct for multiple comparisons.Results: Western blot analysis confirmed the efficacy of transductions with Ad-E2F-1 and Ad-p53. Ad-E2F-1 transduction significantly enhanced apoptosis and decreased clonogenic survival in both cell lines. These effects were compounded by the addition of RT. Although E2F-1-mediated radiosensitization was independent of p53 status, this effect was more pronounced in p53 wild-type LNCaP cells. When PC3 cells were treated with Ad-p53 in combination with RT and Ad-E2F-1, there was at least an additive reduction in clonogenic survival.Conclusions: Our results suggest that Ad-E2F-1 significantly enhances the response of p53 wild-type and p53 null prostate cancer cells to radiation therapy, although radiosensitization is more pronounced in the presence of p53. Ad-E2F-1 may be a useful adjunct to radiation therapy in the treatment of prostate cancer. (c) 2005 Elsevier Inc.