Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Institute of Life Science, Chongqing Medical University, Chongqing, China.
PLoS One. 2014 Jun 6;9(6):e98764. doi: 10.1371/journal.pone.0098764. eCollection 2014.
In order to understand the molecular mechanisms of Bifidobacterium infantis thymidine kinase/nucleoside analogue ganciclovir (BI-TK/GCV) treatment system which was proven to exhibit sustainable anti-tumor growth activity and induce apoptosis in bladder cancer, a proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. 192 down-regulated and 210 up-regulated proteins were identified after treatment with BI-TK/GCV system in Sprague-Dawley (SD) rats. Western blot analysis and immunohistochemistry analysis confirmed that Peroxiredoxin-I (Prx-I) was significantly down-regulated in bladder cancer after treatment. Prx-I silencing by transfection of Prx-I shRNA significantly suppressed growth, promoted apoptosis and regulated the cell cycle in T24 cells and reduced the phospho-NF-κB p50 and p65 protein expression which revealed the links between Prx-I and NF-κB pathway implied by Ingenuity pathway analysis (IPA). These findings yield new insights into the therapy of bladder cancer, revealing Prx-I as a new therapeutic target and indicating BI-TK/GCV system as a prospective therapy by down-regulation of Prx-I through NF-κB signaling pathway.
为了了解双歧杆菌胸苷激酶/核苷类似物更昔洛韦（BI-TK/GCV）治疗系统的分子机制，该系统已被证明在膀胱癌中具有持续的抗肿瘤生长活性和诱导细胞凋亡的作用，我们采用了同位标记相对和绝对定量（iTRAQ）的蛋白质组学方法，随后进行液相色谱-串联质谱（LC-MS/MS）分析。BI-TK/GCV 系统处理 SD 大鼠后，鉴定出 192 个下调蛋白和 210 个上调蛋白。Western blot 分析和免疫组织化学分析证实，膀胱癌治疗后过氧化物还原酶-I（Prx-I）显著下调。Prx-I shRNA 转染沉默 Prx-I 可显著抑制 T24 细胞的生长，促进细胞凋亡和调节细胞周期，并降低磷酸化 NF-κB p50 和 p65 蛋白表达，这揭示了 IPA 分析提示的 Prx-I 与 NF-κB 通路之间的联系。这些发现为膀胱癌的治疗提供了新的见解，揭示了 Prx-I 作为一个新的治疗靶点，并表明 BI-TK/GCV 系统通过 NF-κB 信号通路下调 Prx-I 具有潜在的治疗作用。
